Department of Pediatrics, McGill University, Montreal, Québec, Canada.
Genes Immun. 2009 Dec;10 Suppl 1(Suppl 1):S27-32. doi: 10.1038/gene.2009.88.
The Type I Diabetes Genetics Consortium genotyped 24 single-nucleotide polymorphisms (SNPs) in the CTLA4 locus in 2298 type I diabetes (T1D) nuclear families (11 159 individuals, 5003 affected) to evaluate the recognized T1D association. The 24 CTLA4 SNPs span approximately 43 kb from the 5' flanking to 3' flanking region of the gene in the middle of an extended region of linkage disequilibrium of more than 100 kb. The genotyping was performed using two technologies (Illumina GoldenGate and Sequenom iPlex) on the same samples. The genotype calls by both the methods were highly consistent (the majority >99%). Previously reported T1D association from both the +49G>A and the CT60 SNPs was replicated. The reported association of the -319C>T SNP was not replicated. Although associated with T1D risk, it is likely that neither SNP is causative, as the peak of T1D association was from the SNP rs231727 at 3' flanking of the CTLA4 gene. Comprehensive resequencing and fine mapping of the CTLA4 region are still needed to clarify the causal variants.
I 型糖尿病遗传学联合会（Type I Diabetes Genetics Consortium）在 2298 个 I 型糖尿病（T1D）核心家系（共 1159 个人，5003 名患者）中对 CTLA4 基因座中的 24 个单核苷酸多态性（SNP）进行了基因分型，以评估已确认的 T1D 关联。这 24 个 CTLA4 SNPs 跨越了该基因的 5'侧翼到 3'侧翼区域，大约 43kb，位于超过 100kb 的连锁不平衡扩展区域的中间。基因分型使用了两种技术（Illumina GoldenGate 和 Sequenom iPlex）在相同的样本上进行。两种方法的基因型呼叫高度一致（大多数 >99%）。之前报道的来自 +49G>A 和 CT60 SNPs 的 T1D 关联得到了复制。先前报道的 -319C>T SNP 的关联没有得到复制。尽管与 T1D 风险相关，但这两个 SNP 都不太可能是致病的，因为 T1D 关联的峰值来自 CTLA4 基因 3'侧翼的 SNP rs231727。仍需要对 CTLA4 区域进行全面的重测序和精细定位，以阐明致病变体。
