title: Evaluation of IL12B as a candidate type I diabetes susceptibility gene using data from the Type I Diabetes Genetics Consortium.
abstract: As part of its efforts to identify genes affecting the risk of type I diabetes (T1D), the Type I Diabetes Genetics Consortium commissioned an extensive survey of variants associated with genes reported earlier to have an association with disease susceptibility. In this report, we present the analysis of a set of single-nucleotide polymorphisms (SNPs) within and flanking the IL12B gene, which encodes the p40 subunit of the cytokines interleukin (IL)-12 and IL-23. No SNP showed individually significant association in the population as a whole. Nevertheless, subjects stratified according to genotype at the earlier reported SNP in the IL12B 3'UTR, rs3212227, confirmed small, but significant, differences in age of disease onset with a relative hazard=0.88 (P=0.005). The protective effect of rs3212227 allele 2 was gender specific (P=0.004 overall and P=0.0003 when unaffected siblings were considered). Among females, the 2.2 genotype was more protective, with relative hazard=0.75. We conclude that while there was no major effect of IL12B polymorphisms on T1D susceptibility in the entire study group, they have an impact on a subset of at-risk individuals.
authors: Centre for Diabetes Research, The Western Australian Institute for Medical Research, and Centre for Medical Research, University of Western Australia, 50 Murray Street, Perth, Western Australia 6000, Australia. gem@waimr.uwa.edu.au
authors: G
authors: G
authors: Morahan
authors: E
authors: E
authors: McKinnon
authors: J
authors: J
authors: Berry
authors: B
authors: B
authors: Browning
authors: C
authors: C
authors: Julier
authors: F
authors: F
authors: Pociot
authors: I
authors: I
authors: James
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053762:Interleukin-12 Subunit p40 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012727:Sex Characteristics; D012737:Sex Factors; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40