Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children's Hospital), 2300 Tupper, Montréal, Québec, Canada.
Genes Immun. 2009 Dec;10 Suppl 1(Suppl 1):S42-8. doi: 10.1038/gene.2009.90.
To confirm and fine map previous reports of association, the Type I Diabetes (T1D) Genetics Consortium (T1DGC) assembled a large collection of DNA samples from affected sib-pair (ASP) families with T1D (5003 affected individuals) and genotyped polymorphic markers. One of these loci, involving the IL2RA gene, had been reported to be due to three independent effects. The T1DGC genotyped 69 single-nucleotide polymorphisms (SNPs) that span approximately 88 kb from the 5' flanking to 3' flanking region of the IL2RA locus. The most highly associated SNP reported earlier (ss52580101) was not included in the genotyping list; however, a 5-SNP (rs3134883, rs3118470, rs7072793, rs4749955 and rs12251307) haplotype (H5) was identified that strongly tagged its minor allele with r(2)=0.869 (95% CI, 0.850-0.885). This haplotype was significantly protective (P=3.2 x 10(-5)) in the T1D ASP families, with an odds ratio virtually identical to that reported for ss52580101. The SNP marking the second independent locus, (rs11594656) showed no association in the T1DGC set and the third (rs2104286) could not be distinguished, by conditional regression, from H5. Instead, the most significant independent effect was detected from the 5' flanking IL2RA SNP rs4749955, which remained significant after regression for H5. Thus, we confirm independent effects at the IL2RA locus.
为了确认并精确定位之前有关关联的报告，I 型糖尿病（T1D）遗传学联合会（T1DGC）收集了大量 T1D 受影响同胞对（ASP）家庭的 DNA 样本（5003 名受影响个体），并对多态性标记进行了基因分型。其中一个涉及 IL2RA 基因的位点，据报道，它是由三个独立的效应引起的。T1DGC 对 IL2RA 基因座的 5'侧翼到 3'侧翼区域约 88kb 范围内的 69 个单核苷酸多态性（SNP）进行了基因分型。之前报告的相关性最高的 SNP（ss52580101）未包含在基因分型列表中；然而，鉴定出了一个 5-SNP（rs3134883、rs3118470、rs7072793、rs4749955 和 rs12251307）单体型（H5），其与次要等位基因的 r(2)=0.869（95%置信区间，0.850-0.885）紧密相关。该单体型在 T1D ASP 家族中具有显著的保护作用（P=3.2 x 10(-5)），其优势比与 ss52580101 报告的几乎相同。标记第二个独立位点的 SNP（rs11594656）在 T1DGC 组中没有关联，第三个（rs2104286）不能通过条件回归与 H5 区分开来。相反，在 IL2RA 基因座的 5'侧翼 SNP rs4749955 中检测到最显著的独立效应，该效应在回归 H5 后仍然显著。因此，我们确认了 IL2RA 基因座的独立效应。
