Owerbach D, Gabbay K H
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Diabetes. 1995 Jan;44(1):132-6. doi: 10.2337/diab.44.1.132.
Type I diabetes susceptibility genes have been identified within the major histocompatibility complex (MHC) on chromosome 6p21.3 and near the VNTR/insulin region on chromosome 11p15.5. We have used polymorphic dinucleotide repeat markers to search the human genome for additional susceptibility genes in 162 type I diabetic families with an affected sibling pair. We report that an additional susceptibility gene is located on chromosome 2q31 near HOXD8 (P < 10(-5), maximum logarithm of odds score = 4.8) in an analysis of affected sibling pairs having specific human leukocyte antigen (HLA) and hypervariable nucleotide tandem repeat (VNTR)/insulin gene haplotypes (absence of high-risk HLA-DR3/4 haplotypes and presence of homozygous high-risk class I VNTR alleles). These results suggest the interaction of a minimum of three genes in the pathogenesis of type I diabetes in humans.
1型糖尿病易感基因已在6号染色体p21.3的主要组织相容性复合体（MHC）内以及11号染色体p15.5的VNTR/胰岛素区域附近被鉴定出来。我们利用多态性二核苷酸重复标记，在162个有患病同胞对的1型糖尿病家族中搜索人类基因组中的其他易感基因。我们报告称，在对具有特定人类白细胞抗原（HLA）和高变核苷酸串联重复序列（VNTR）/胰岛素基因单倍型（不存在高危HLA-DR3/4单倍型且存在纯合高危I类VNTR等位基因）的患病同胞对进行分析时，另一个易感基因位于2号染色体q31靠近HOXD8的位置（P < 10^(-5)，最大优势对数分数 = 4.8）。这些结果表明，在人类1型糖尿病发病机制中至少有三个基因相互作用。
