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Article |

Polymorphisms for Interleukin 1β Exon 5 and Interleukin 1 Receptor Antagonist in Taiwanese Children With Febrile Convulsions FREE

Fuu-Jen Tsai, MD, PhD; Yao-Yuan Hsieh, MD; Chi-Chen Chang, MD; Cheng-Chieh Lin, MD; Chang-Hai Tsai, MD, PhD
[+] Author Affiliations

From the Departments of Pediatrics and Medical Genetics (Drs F.-J. Tsai and C.-H. Tsai), Obstetrics and Gynecology (Drs Hsieh and Chang), and Family Medicine (Dr Lin), China Medical College Hospital, Taichung, Taiwan.


Arch Pediatr Adolesc Med. 2002;156(6):545-548. doi:10.1001/archpedi.156.6.545.
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Published online

Objective  To investigate whether interleukin 1β (IL-1β) exon 5 and IL-1 receptor antagonist (IL-1Ra) gene polymorphisms can be used as markers of susceptibility to febrile convulsions in children.

Methods  Children were divided into 2 groups: those with febrile convulsions (group 1; n = 51) and normal control subjects (group 2; n = 83). Polymorphisms for IL-1β exon 5 and IL-1Ra gene polymorphisms were detected by polymerase chain reaction. Genotypes and allelic frequencies for IL-1β exon 5 and IL-1Ra gene polymorphisms in both groups were compared.

Results  Genotype and allele frequencies for IL-1β exon 5 in both groups were not significantly different. Proportions of E1 homozygotes and E1/E2 heterozygotes for IL-1β exon 5 were 50 (98.1%) and 1 (1.9%), respectively, in group 1 and 82 (98.8%) and 1 (1.2%), respectively, in group 2. Frequencies of alleles E1 and E2 for IL-1β exon 5 were 101 (99.0%) and 1 (1.0%), respectively, in group 1 and 165 (99.4%) and 1 (0.6%), respectively, in group 2. Genotype proportions and allele frequencies for IL-1Ra between groups were significantly different. Proportions of genotypes I/I and I/II for IL-1Ra were 49 (96.1%) and 2 (3.9%) in group 1 and 69 (83.1%) and 14 (16.9%) in group 2. Frequencies of alleles I and II for IL-1Ra were 100 (98.0%) and 2 (2.0%) in group 1 and 152 (91.6%) and 14 (8.4%) in group 2.

Conclusions  The IL-1Ra allele I is associated with a higher susceptibility to febrile convulsion, which may become a useful marker for predicting the development of febrile convulsions. The IL-1β exon 5 gene polymorphisms are not a useful marker for predicting the susceptibility to febrile convulsions.

FEBRILE CONVULSIONS, the most common form of childhood seizures, occur in 2% to 5% of children before the age of 5 years.1 Febrile convulsions are marked by high or rapidly rising fever and short duration; uncomplicated convulsions do not predispose to epilepsy and are not associated with neurologic abnormalities.2 The pathogenesis of febrile convulsions remains obscure. Possible causes include viral infection of the central nervous system and lowered threshold for convulsions in the presence of fever.3 Recently, febrile convulsions have been suggested to be a gene-related disease.4 In fact, febrile convulsions of children involve a complex interaction between the immunoinflammatory process, cytokine activation, and genetic factors.5

Cytokine is a key factor of the host response to infection, and its effects include induction of fever, leukocytosis, and acute-phase protein synthesis.6 Cells from children prone to seizures may produce more proinflammatory cytokines that may induce convulsions or, alternatively, higher levels of anti-inflammatory cytokines as a defense mechanism against seizure.7 Proinflammatory cytokines, including interleukin 1β (IL-1β), are known to modulate effects of neurotoxic neurotransmitters discharged during excitation or inflammation in the central nervous system.8 Some cytokine polymorphisms might be related to febrile convulsions, including IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1Ra) gene polymorphisms.8 Interleukin 1 belongs to a cytokine family modulating cellular proliferation and has the capacity to induce other cytokines. It is a primary mediator of the inflammatory response and has been shown to induce prostaglandin synthesis.9

The IL-1 genes are associated with several immunoinflammatory diseases.10 The IL-1β polymorphisms are associated with enhanced production of IL-1β and the increased risk of both hypochlorhydria induced by Helicobacter pylori and gastric cancer.11 The IL-1β polymorphisms were related to the regulation of cytokine and growth factor expression in articular chondrocytes and the final development of osteoarthritis.12 Allele E2 in IL-1β exon 5 was related to an increased risk of erosive arthritis.13 The action of IL-1 is complex and regulated in part by its naturally occurring inhibitor, the IL-1Ra.

Genetic studies of multifactorial diseases such as febrile convulsions are difficult to approach because of the uncertainty of polygenic traits. In our laboratory, we have observed that the IL-1β-511*T allele could be used as a genetic marker of susceptibility to Kawasaki disease (Yi-Ru Shi, MS, F.-J.T., and C.-H.T., unpublished data, 2001). In contrast, we noted that the IL-1β (IL-1β-511 promotor, IL-1β exon 5) and IL-1Ra were not useful markers to predict susceptibility to endometriosis and rheumatoid arthritis.14 We also noted that the IL-1β-511 promotor polymorphism is not a useful marker for prediction of the susceptibility to febrile convulsions and epilepsy (F.-J.T., Y.-Y.H., C.-C.C., and C.-H.T., unpublished data, 2001). On the basis of these experiences, we further tried to evaluate whether these polymorphisms are useful markers for predicting susceptibility to febrile convulsions in children.

The study included Taiwanese children with febrile convulsions (group 1; n = 51) and normal control subjects (group 2; n = 83). This study was approved by the Ethical Committee of the China Medical College Hospital, Taichung, Taiwan. Informed consent was signed by all parents of the patients who donated their blood. There were nonsignificant differences between the groups in age, weight, and height. The diagnosis of febrile convulsions was made after the exclusion of other causative agents, including bacterial or viral infection.

All children underwent peripheral blood sampling for genotype analyses. Genomic DNA was isolated from peripheral blood by means of a DNA extractor kit (Genomaker DNA extraction kit; Blossom, Taiwan). A total of 50 ng of genomic DNA was mixed with 20 pmol of each polymerase chain reaction (PCR) primer in a total volume of 25 µL containing 10mM Tris hydrochloride, pH 8.3; 50mM potassium chloride; 2.0mM magnesium chloride; 0.2mM each deoxyribonucleotide triphosphate; and 1 U of DNA polymerase (Amplitaq; Perkin-Elmer, Foster City, Calif). Four PCR primers were used to amplify the correlated gene. The sequences of these primers were as following (from 5′ to 3′ end): IL-1β exon 5: upstream, GTTGTCATCAGACTTTGACC; downstream, TTCAGTTCATATGGACCAGA; and IL-1Ra: upstream, CTCAGCAACACTCCTAT; downstream, TCCTGGTCTGCAGGTAA. The PCR conditions were as follows: 35 cycles at 94°C for 1 minute, 60°C for 1 minute, and 72°C for 2 minutes, then stand at 72° for 30 minutes and hold at 4°. Biallelic base polymorphisms in exon 5 at position +3953 (IL-1β+3953) for IL-1β gene were detected. The IL-1β+3953 exon 5 polymorphism was analyzed by PCR amplification followed by Taq I restriction analysis.15 The PCR products were directly analyzed for IL-1Ra by electrophoresis on agarose gel, and each allele was recognized according to its size. Allelic frequencies are expressed as a percentage of the total number of alleles. Genotypes and allelic frequencies for IL-1β and IL-1Ra polymorphisms in both groups were compared.

The SAS system with χ2 and Fisher exact test were used for statistical analyses. P<.05 was considered statistically significant.

Genotype proportions and allele frequencies for IL-1β exon 5 in both groups were not significantly different (Table 1). The most common genotype for IL-1 gene in both groups was E1 homozygote. Proportions of E1 homozygote and E1/E2 heterozygote for IL-1β exon 5 were as follows: group 1, 98.0% and 1.9%, respectively; group 2, 98.8% and 1.2%, respectively. There were no E2 homozygotes. Allele E1 and E2 frequencies for IL-1β exon 5 were as follows: group 1, 99.0% and 1.0%, respectively; group 2, 99.4% and 0.6%, respectively (Table 1).

Table Graphic Jump LocationTable 1. Genotypes and Allele Frequency of IL-1β Exon 5 in Children With Febrile Convulsions and Normal Control Subjects*

In contrast, the genotype proportions and allele frequencies for IL-1Ra between the groups were significantly different. The most common genotype for IL-1 gene in both groups was I/I. Proportions of I/I and I/II for IL-1Ra were as follows: group 1, 96.1% and 3.9%, respectively; group 2, 83.1% and 16.9%, respectively (Table 2). Allele I for IL-1Ra was associated with febrile convulsions. Allele I/II for IL-1Ra was found in the following proportions: group 1, 98.0% and 2.0%, respectively; group 2, 91.6% and 8.4%, respectively (Table 2).

Table Graphic Jump LocationTable 2. Genotypes and Allele Frequency of IL-1 Receptor Antagonist in Children With Febrile Convulsions and Normal Control Subjects*

Cytokines are proteins that play a role in the communication link between the immunologic system and brain tissue. Cytokines are related to leukocyte function and migration, angiogenesis, hematopoiesis, antitumoral effects, and atherosclerosis.16 They are produced by peripheral monocytes and also by astrocytes and glial cells within the central nervous system.17 Cytokines from peripheral-blood mononuclear cells may cross the blood-brain barrier and may thus be involved in the pathogenesis of fever.18

The IL-1 response from sensitized mononuclear cells may have a role in the development of febrile convulsions.3 During the acute phase of febrile convulsions, patients have significantly increased plasma IL-1β levels, which may be responsible for the pathogenesis of febrile convulsions.18 Differences in the distribution of the biallelic polymorphism in the promotor region of the IL-1β gene were found among patients exhibiting temporal lobe epilepsy.8 Interleukin 1 also regulates the development of glial scars at sites of central nervous system injury.8 In contrast, Ichiyama et al19 found no correlation between the cytokines tumor necrosis factor α, IL-1β, and IL-6 in the cerebrospinal fluid and the presence of febrile seizures.

Genetic factors play a major role in the etiology of febrile convulsions. Cytokine genes may be related to cytokine expression and regulation of the immune-mediated pathogenetic process. Cytokine gene polymorphisms have recently attracted considerable interest because distinct alleles of cytokine genes have been discovered to be associated with different immunoinflammatory diseases.7 Single nucleotide polymorphisms are the most abundant types of DNA sequence variation in the human genome.20 Single nucleotide polymorphism markers provide a new way to identify complex gene-associated diseases such as febrile convulsions in children.

Interleukin 1 exists in 2 forms, IL-1α and IL-1β, which are encoded by distinct genes but share the same receptors and biological properties.21 The loci for IL-1α and IL-1β are located on the proximal region of the long arm of chromosome 2.22 The IL-1β polymorphism has been correlated with IL-1β expression.23 These results indicate that the genotype of the IL-1β polymorphisms may affect IL-1β production in an intricate and complicated manner. Different polymorphisms have been described in the IL-1β gene, and at least 2 of them could influence protein production: one located in the promotor region at position -511 (IL-1β-511)12 and the other in exon 5.15 In our previous research, we noted the lack of association between febrile convulsions and IL-1β-511 promotor polymorphism (F.-J.T., Y.-Y.H., C.-C.C., and C.-H.T., unpublished data, 2001). These genes code several proteins that may be key components in the pathogenesis of febrile convulsions.

The IL-1 or IL-1Ra polymorphisms have been found to be related to susceptibility or disease activities for individual diseases, including Alzheimer disease,24 Parkinson disease,25 temporal lobe epilepsy,8 schizophrenia,26 erosive arthritis,13 polymyositis and dermatomyositis,27 multiple sclerosis,28 lymphocytic leukemia,29 atherosclerosis,30 coronary artery disease,31 alcoholic liver disease,32 idiopathic pancreatitis,33 inflammatory bowel disease,34 and IgA nephropathy.35 The regulation of IL-1β and IL-1Ra may be coordinated during inflammation.36 The level of IL-1β messenger RNA showed a positive correlation with that of IL-1β and a negative correlation with the level of IL-1Ra messenger RNA.37

In contrast, some investigators have found no correlation between genetic polymorphisms of IL-1β and susceptibility to rheumatoid arthritis,13 chronic obstructive pulmonary disease,38 multiple myeloma,39 diabetes mellitus,40 postmenopausal osteoporosis,41 and ischemic heart disease.42 Furthermore, IL-1 genes may have a role in the severity of the disease rather than in susceptibility to the disease itself.10 In our previous study, we also observed an association between disease activity of rheumatoid arthritis and a polymorphic IL-1β–511*C gene sequence (Chun-Ming Huang, MD, F.-J.T., and C.-H.T., unpublished data, 2001).

The IL-1Ra is structurally related to IL-1α and IL-1β and competes with these molecules for occupation of IL-1 cell surface receptors. The presence of the IL-1Ra allele II was associated with enhanced IL-1β production in vitro.43 The IL-1Ra allele II is associated with a variety of epithelial-related chronic inflammatory diseases including systemic lupus erythematosus,44 psoriasis,45 alopecia areata,46 lichen sclerosus,47 and ulcerative colitis.48 In this study, we observed that the IL-1Ra allele I is associated with higher susceptibility to febrile convulsions. The results further suggest that the IL-1Ra allele II as well as the increased production of IL-1β might play a role in preventing febrile convulsions. Genotype distributions and allelic frequencies for IL-1Ra gene polymorphism may be the candidate genetic markers in the susceptibility to febrile convulsion. In contrast, the IL-1β exon 5 gene polymorphism is not useful in predicting the susceptibility to febrile convulsion. This discrepancy may be due to different illness classifications and racial and disease variation.

In conclusion, IL-1Ra is a useful marker for predicting susceptibility to febrile convulsions. In contrast, febrile convulsions are not associated with IL-1β exon 5 gene polymorphisms. This could provide the database for further survey of the IL-1 and IL-1Ra polymorphisms. However, the real roles of the IL-1 polymorphisms in febrile convulsions remain to be clarified. Furthermore, the impact of other cytokine polymorphisms on development of febrile convulsions merits further study.

Accepted for publication February 7, 2002.

What This Study Adds

Interleukin 1β exon 5 and IL-1Ra may be related to the pathogenesis of febrile convulsions. This study examines the potential usefulness of these markers in predicting susceptibility to febrile convulsions in children. We found that interleukin 1 receptor antagonist is a useful marker for predicting susceptibility to febrile convulsions.

Corresponding author and reprints: Fuu-Jen Tsai, MD, PhD, Department of Pediatrics and Medical Genetics, China Medical College Hospital, No. 2 Yuh-Der Rd, Taichung, Taiwan (e-mail: d0704@hpd.cmch.org.tw).

Wallace  RHWang  DWSingh  R  et al.  Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19366- 370
Link to Article
Addy  DP Nosology of febrile convulsions. Arch Dis Child. 1986;61318- 320
Link to Article
Helminen  MVesikari  T Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand. 1990;79810- 816
Link to Article
Johnson  EWDubovsky  JRich  SS  et al.  Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest. Hum Mol Genet. 1998;763- 67
Link to Article
Vigano  PGaffuri  BSomigliana  EBusacca  MDi Blasio  AMVignali  M Expression of intercellular adhesion molecule (ICAM)–1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod. 1998;41150- 1156
Link to Article
Florman  AL Interleukin-1 and monitoring of acute infections. Pediatr Infect Dis. 1985;4450- 452
Link to Article
Straussberg  RAmir  JHarel  LPunsky  IBessler  H Pro- and anti-inflammatory cytokines in children with febrile convulsions. Pediatr Neurol. 2001;2449- 53
Link to Article
Kanemoto  KKawasaki  JMiyamoto  TObayashi  HNishimura  M Interleukin (IL) 1beta, IL-1alpha, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy. Ann Neurol. 2000;47571- 574
Link to Article
Rossi  VBreviario  FGhezzi  PDejana  EMontovani  A Prostacyclin synthesis induced by vascular cells by interleukin-1. Science. 1985;229174- 176
Link to Article
Demeter  JMesser  GRamisch  S  et al.  Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies. Cytokines Mol Ther. 1996;2239- 242
El-Omar  EMCarrington  MChow  WH  et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404398- 402
Link to Article
Moos  VRudwaleit  MHerzog  VHohlig  KSieper  JMuller  B Association of genotypes affecting the expression of interleukin-1beta or interleukin-1 receptor antagonist with osteoarthritis. Arthritis Rheum. 2000;432417- 2422
Link to Article
Cantagrel  ANavaux  FLoubet-Lescoulie  P  et al.  Interleukin-1β, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum. 1999;421093- 1100
Link to Article
Hsieh  YYChang  CCTsai  FJ  et al.  Polymorphisms for interleukin-1 beta (IL-1 beta)-511 promotor, IL-1 beta exon 5, and IL-1 receptor antagonist: nonassociation with endometriosis. J Assist Reprod Genet. 2001;18506- 511
Link to Article
Pociot  FMolvig  JWogensen  L  et al.  A TaqI polymorphism in the human interleukin-1β (IL-1β) gene correlates with IL-1β secretion in vitro. Eur J Clin Invest. 1992;22396- 402
Link to Article
Garcia-Velasco  JAArici  A Chemokines and human reproduction. Fertil Steril. 1999;71983- 993
Link to Article
Dinarello  CA Interleukin 1. Rev Infect Dis. 1984;651- 95
Link to Article
Tutuncuoglu  SKutukculer  NKepe  LCoker  CBerdeli  ATekgul  H Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int. 2001;43235- 239
Link to Article
Ichiyama  TNishikawa  MYoshitomi  THayashi  TFurukawa  S Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures: comparison with acute encephalitis/encephalopathy. Neurology. 1998;50407- 411
Link to Article
Kwok  PYGu  Z Single nucleotide polymorphism libraries: why and how are we building them? Mol Med Today. 1999;5538- 543
Link to Article
Robertson  SASeamark  RF The role of cytokines in gestation. Crit Rev Immunol. 1994;14239- 292
Link to Article
Copeland  NGSilan  CMKingsley  DM  et al.  Chromosomal location of murine and human IL-1 receptor genes. Genomics. 1991;944- 50
Link to Article
Mark  LLHaffajee  ADSocransky  SS  et al.  Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects with adult periodontitis. J Periodontal Res. 2000;35172- 177
Link to Article
Licastro  FPedrini  SFerri  C  et al.  Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer's disease risk. Ann Neurol. 2000;48388- 391
Link to Article
Nishimura  MMizuta  IMizuta  EYamasaki  SOhta  MKuno  S Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson's disease. Neurosci Lett. 2000;28473- 76
Link to Article
Katila  HHanninen  KHurme  M Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry. 1999;4179- 181
Link to Article
Son  KTomita  YShimizu  TNishinarita  SSawada  SHorie  T Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis. Intern Med. 2000;39128- 135
Link to Article
Kantarci  OHAtkinson  EJHebrink  DDMcMurray  CTWeinshenker  BG Association of two variants in IL-1beta and IL-1 receptor antagonist genes with multiple sclerosis. J Neuroimmunol. 2000;106220- 227
Link to Article
Hulkkonen  JVilpo  JVilpo  LKoski  THurme  M Interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-6 plasma levels and cytokine gene polymorphisms in chronic lymphocytic leukemia: correlation with prognostic parameters. Haematologica. 2000;85600- 606
Dewberry  RHolden  HCrossman  DFrancis  S Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;202394- 2400
Link to Article
Francis  SECamp  NJDewberry  RM  et al.  Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation. 1999;99861- 866
Link to Article
Takamatsu  MYamauchi  MMaezawa  YSaito  SMaeyama  SUchikoshi  T Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients. Am J Gastroenterol. 2000;951305- 1311
Smithies  AMSargen  KDemaine  AGKingsnorth  AN Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis. Pancreas. 2000;20234- 240
Link to Article
Nemetz  AKope  AMolnar  T  et al.  Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease. Scand J Gastroenterol. 1999;34175- 179
Link to Article
Shu  KHLee  SHCheng  CHWu  MJLian  JD Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphism on IgA nephropathy. Kidney Int. 2000;58783- 789
Link to Article
Hurme  MSanttila  S IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;282598- 2602
Link to Article
Mori  HSawairi  MNakagawa  MItoh  NWada  KTamaya  T Expression of interleukin-1 (IL-1) beta messenger ribonucleic acid (mRNA) and IL-1 receptor antagonist mRNA in peritoneal macrophages from patients with endometriosis. Fertil Steril. 1992;57535- 542
Ishii  TMatsuse  TTeramoto  S  et al.  Neither IL-1beta, IL-1 receptor antagonist, nor TNF-alpha polymorphisms are associated with susceptibility to COPD. Respir Med. 2000;94847- 851
Link to Article
Zheng  CHuang  DRBergenbrant  S  et al.  Interleukin 6, tumour necrosis factor alpha, interleukin 1beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol. 2000;10939- 45
Link to Article
Kristiansen  OPPociot  FJohannesen  J  et al.  Linkage disequilibrium testing of four interleukin-1 gene-cluster polymorphisms in Danish multiplex families with insulin-dependent diabetes mellitus. Cytokine. 2000;12171- 175
Link to Article
Bajnok  ETakacs  IVargha  PSpeer  GNagy  ZLakatos  P Lack of association between interleukin-1 receptor antagonist protein gene polymorphism and bone mineral density in Hungarian postmenopausal women. Bone. 2000;27559- 562
Link to Article
Manzoli  AAndreotti  FVarlotta  C  et al.  Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia. 1999;44825- 830
Santtila  SSavinainen  KHurme  M Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol. 1998;47195- 198
Link to Article
Blakemore  AIFTarlow  JKCork  MJGordon  CEmery  PDuff  GW Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis Rheum. 1994;371380- 1385
Link to Article
Tarlow  JKCork  MJClay  FE  et al.  Association between interleukin-1 receptor antagonist gene polymorphism and early and late-onset psoriasis. Br J Dermatol. 1997;136147- 148
Link to Article
Tarlow  JKClay  FECork  MJ  et al.  Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene. J Invest Dermatol. 1994;103387- 390
Link to Article
Clay  FECork  MJTarlow  JK  et al.  Interleukin-1 receptor antagonist gene polymorphism association with lichen sclerosus. Hum Genet. 1994;94407- 410
Link to Article
Mansfield  JCHolden  HTarlow  JK  et al.  Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology. 1994;106637- 642

Figures

Tables

Table Graphic Jump LocationTable 1. Genotypes and Allele Frequency of IL-1β Exon 5 in Children With Febrile Convulsions and Normal Control Subjects*
Table Graphic Jump LocationTable 2. Genotypes and Allele Frequency of IL-1 Receptor Antagonist in Children With Febrile Convulsions and Normal Control Subjects*

References

Wallace  RHWang  DWSingh  R  et al.  Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998;19366- 370
Link to Article
Addy  DP Nosology of febrile convulsions. Arch Dis Child. 1986;61318- 320
Link to Article
Helminen  MVesikari  T Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand. 1990;79810- 816
Link to Article
Johnson  EWDubovsky  JRich  SS  et al.  Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest. Hum Mol Genet. 1998;763- 67
Link to Article
Vigano  PGaffuri  BSomigliana  EBusacca  MDi Blasio  AMVignali  M Expression of intercellular adhesion molecule (ICAM)–1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod. 1998;41150- 1156
Link to Article
Florman  AL Interleukin-1 and monitoring of acute infections. Pediatr Infect Dis. 1985;4450- 452
Link to Article
Straussberg  RAmir  JHarel  LPunsky  IBessler  H Pro- and anti-inflammatory cytokines in children with febrile convulsions. Pediatr Neurol. 2001;2449- 53
Link to Article
Kanemoto  KKawasaki  JMiyamoto  TObayashi  HNishimura  M Interleukin (IL) 1beta, IL-1alpha, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy. Ann Neurol. 2000;47571- 574
Link to Article
Rossi  VBreviario  FGhezzi  PDejana  EMontovani  A Prostacyclin synthesis induced by vascular cells by interleukin-1. Science. 1985;229174- 176
Link to Article
Demeter  JMesser  GRamisch  S  et al.  Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies. Cytokines Mol Ther. 1996;2239- 242
El-Omar  EMCarrington  MChow  WH  et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404398- 402
Link to Article
Moos  VRudwaleit  MHerzog  VHohlig  KSieper  JMuller  B Association of genotypes affecting the expression of interleukin-1beta or interleukin-1 receptor antagonist with osteoarthritis. Arthritis Rheum. 2000;432417- 2422
Link to Article
Cantagrel  ANavaux  FLoubet-Lescoulie  P  et al.  Interleukin-1β, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum. 1999;421093- 1100
Link to Article
Hsieh  YYChang  CCTsai  FJ  et al.  Polymorphisms for interleukin-1 beta (IL-1 beta)-511 promotor, IL-1 beta exon 5, and IL-1 receptor antagonist: nonassociation with endometriosis. J Assist Reprod Genet. 2001;18506- 511
Link to Article
Pociot  FMolvig  JWogensen  L  et al.  A TaqI polymorphism in the human interleukin-1β (IL-1β) gene correlates with IL-1β secretion in vitro. Eur J Clin Invest. 1992;22396- 402
Link to Article
Garcia-Velasco  JAArici  A Chemokines and human reproduction. Fertil Steril. 1999;71983- 993
Link to Article
Dinarello  CA Interleukin 1. Rev Infect Dis. 1984;651- 95
Link to Article
Tutuncuoglu  SKutukculer  NKepe  LCoker  CBerdeli  ATekgul  H Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int. 2001;43235- 239
Link to Article
Ichiyama  TNishikawa  MYoshitomi  THayashi  TFurukawa  S Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures: comparison with acute encephalitis/encephalopathy. Neurology. 1998;50407- 411
Link to Article
Kwok  PYGu  Z Single nucleotide polymorphism libraries: why and how are we building them? Mol Med Today. 1999;5538- 543
Link to Article
Robertson  SASeamark  RF The role of cytokines in gestation. Crit Rev Immunol. 1994;14239- 292
Link to Article
Copeland  NGSilan  CMKingsley  DM  et al.  Chromosomal location of murine and human IL-1 receptor genes. Genomics. 1991;944- 50
Link to Article
Mark  LLHaffajee  ADSocransky  SS  et al.  Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects with adult periodontitis. J Periodontal Res. 2000;35172- 177
Link to Article
Licastro  FPedrini  SFerri  C  et al.  Gene polymorphism affecting alpha1-antichymotrypsin and interleukin-1 plasma levels increases Alzheimer's disease risk. Ann Neurol. 2000;48388- 391
Link to Article
Nishimura  MMizuta  IMizuta  EYamasaki  SOhta  MKuno  S Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson's disease. Neurosci Lett. 2000;28473- 76
Link to Article
Katila  HHanninen  KHurme  M Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry. 1999;4179- 181
Link to Article
Son  KTomita  YShimizu  TNishinarita  SSawada  SHorie  T Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis. Intern Med. 2000;39128- 135
Link to Article
Kantarci  OHAtkinson  EJHebrink  DDMcMurray  CTWeinshenker  BG Association of two variants in IL-1beta and IL-1 receptor antagonist genes with multiple sclerosis. J Neuroimmunol. 2000;106220- 227
Link to Article
Hulkkonen  JVilpo  JVilpo  LKoski  THurme  M Interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-6 plasma levels and cytokine gene polymorphisms in chronic lymphocytic leukemia: correlation with prognostic parameters. Haematologica. 2000;85600- 606
Dewberry  RHolden  HCrossman  DFrancis  S Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;202394- 2400
Link to Article
Francis  SECamp  NJDewberry  RM  et al.  Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation. 1999;99861- 866
Link to Article
Takamatsu  MYamauchi  MMaezawa  YSaito  SMaeyama  SUchikoshi  T Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients. Am J Gastroenterol. 2000;951305- 1311
Smithies  AMSargen  KDemaine  AGKingsnorth  AN Investigation of the interleukin 1 gene cluster and its association with acute pancreatitis. Pancreas. 2000;20234- 240
Link to Article
Nemetz  AKope  AMolnar  T  et al.  Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease. Scand J Gastroenterol. 1999;34175- 179
Link to Article
Shu  KHLee  SHCheng  CHWu  MJLian  JD Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphism on IgA nephropathy. Kidney Int. 2000;58783- 789
Link to Article
Hurme  MSanttila  S IL-1 receptor antagonist (IL-1Ra) plasma levels are co-ordinately regulated by both IL-1Ra and IL-1beta genes. Eur J Immunol. 1998;282598- 2602
Link to Article
Mori  HSawairi  MNakagawa  MItoh  NWada  KTamaya  T Expression of interleukin-1 (IL-1) beta messenger ribonucleic acid (mRNA) and IL-1 receptor antagonist mRNA in peritoneal macrophages from patients with endometriosis. Fertil Steril. 1992;57535- 542
Ishii  TMatsuse  TTeramoto  S  et al.  Neither IL-1beta, IL-1 receptor antagonist, nor TNF-alpha polymorphisms are associated with susceptibility to COPD. Respir Med. 2000;94847- 851
Link to Article
Zheng  CHuang  DRBergenbrant  S  et al.  Interleukin 6, tumour necrosis factor alpha, interleukin 1beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol. 2000;10939- 45
Link to Article
Kristiansen  OPPociot  FJohannesen  J  et al.  Linkage disequilibrium testing of four interleukin-1 gene-cluster polymorphisms in Danish multiplex families with insulin-dependent diabetes mellitus. Cytokine. 2000;12171- 175
Link to Article
Bajnok  ETakacs  IVargha  PSpeer  GNagy  ZLakatos  P Lack of association between interleukin-1 receptor antagonist protein gene polymorphism and bone mineral density in Hungarian postmenopausal women. Bone. 2000;27559- 562
Link to Article
Manzoli  AAndreotti  FVarlotta  C  et al.  Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia. 1999;44825- 830
Santtila  SSavinainen  KHurme  M Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol. 1998;47195- 198
Link to Article
Blakemore  AIFTarlow  JKCork  MJGordon  CEmery  PDuff  GW Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis Rheum. 1994;371380- 1385
Link to Article
Tarlow  JKCork  MJClay  FE  et al.  Association between interleukin-1 receptor antagonist gene polymorphism and early and late-onset psoriasis. Br J Dermatol. 1997;136147- 148
Link to Article
Tarlow  JKClay  FECork  MJ  et al.  Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene. J Invest Dermatol. 1994;103387- 390
Link to Article
Clay  FECork  MJTarlow  JK  et al.  Interleukin-1 receptor antagonist gene polymorphism association with lichen sclerosus. Hum Genet. 1994;94407- 410
Link to Article
Mansfield  JCHolden  HTarlow  JK  et al.  Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology. 1994;106637- 642

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