Mirel Daniel B, Valdes Ana Maria, Lazzeroni Laura C, Reynolds Rebecca L, Erlich Henry A, Noble Janelle A
Department of Human Genetics, Roche Molecular Systems, Alameda, California 94501, USA.
Diabetes. 2002 Nov;51(11):3336-41. doi: 10.2337/diabetes.51.11.3336.
We have investigated, in 282 multiplex Caucasian families (the Human Biological Data Interchange Repository), the association of type 1 diabetes with polymorphisms in the IL4R gene. IL4R encodes a subunit of the interleukin-4 receptor, a molecule critical to T-helper cell development. By genotyping eight different IL4R single-nucleotide polymorphisms (SNPs) and identifying haplotypes (complex alleles) in the multiplex type 1 diabetic families who were stratified for HLA genotype, we have observed significant evidence of linkage and association of the IL4R gene to type 1 diabetes. In particular, we have identified a specific haplotype that appears to be protective and observed that this protective effect is strongest among individuals not carrying the HLA DR3/DR4 genotype (which confers the strongest genetic risk for type 1 diabetes). These findings suggest an important role for the IL4R gene in immune-related disease susceptibility and illustrate the value of using multi-SNP haplotype information in association studies.
我们在282个白种人多重家庭（人类生物数据交换库）中研究了1型糖尿病与IL4R基因多态性之间的关联。IL4R编码白细胞介素-4受体的一个亚基，该分子对辅助性T细胞发育至关重要。通过对8种不同的IL4R单核苷酸多态性（SNP）进行基因分型，并在根据HLA基因型分层的1型糖尿病多重家庭中鉴定单倍型（复合等位基因），我们观察到了IL4R基因与1型糖尿病存在连锁和关联的显著证据。特别是，我们鉴定出了一种似乎具有保护作用的特定单倍型，并观察到这种保护作用在不携带HLA DR3/DR4基因型（赋予1型糖尿病最强遗传风险）的个体中最为明显。这些发现表明IL4R基因在免疫相关疾病易感性中起重要作用，并说明了在关联研究中使用多SNP单倍型信息的价值。
