Department of Endocrinology, Metabolism and Diabetes, Faculty of Medicine, Kindai University, Osaka, Japan.
Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
Diabetes. 2019 Mar;68(3):665-675. doi: 10.2337/db18-0314. Epub 2018 Dec 14.
The first genome-wide association study of fulminant type 1 diabetes was performed in Japanese individuals. As previously reported using a candidate gene approach, a strong association was observed with multiple single nucleotide polymorphisms (SNPs) in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region ( = 1.56 × 10, odds ratio [OR] 3.18). In addition, rs11170445 in on chromosome 12q13.13 showed an association at a genome-wide significance level ( = 7.58 × 10, OR 1.96). Fine mapping of the region revealed that rs3782151 in showed the lowest value ( = 4.60 × 10, OR 1.97 [95% CI 1.57-2.48]). The risk allele of rs3782151 is a expression quantitative trait locus for that significantly increases the expression of this gene. was found to be strongly associated with susceptibility to fulminant, but not classical, autoimmune type 1 diabetes, implicating this locus in the distinct phenotype of fulminant type 1 diabetes.
首例暴发性 1 型糖尿病的全基因组关联研究在日本人群中进行。如之前使用候选基因方法报道的，在 HLA 区域中观察到多个单核苷酸多态性（SNP）与暴发性 1 型糖尿病强烈相关，而在 II 类 DR 区域中的 rs9268853 与暴发性 1 型糖尿病的相关性最强（ = 1.56×10 ，比值比[OR]3.18）。此外，染色体 12q13.13 上的 rs11170445 在全基因组显著水平上与暴发性 1 型糖尿病相关（ = 7.58×10 ，OR 1.96）。该区域的精细映射显示， 上的 rs3782151 显示出最低的 P 值（ = 4.60×10 ，OR 1.97[95%CI1.57-2.48]）。rs3782151 的风险等位基因是一个 表达数量性状基因座，可显著增加该基因的表达。 与暴发性但非经典自身免疫性 1 型糖尿病的易感性强烈相关，表明该基因座与暴发性 1 型糖尿病的独特表型有关。
