Department of Endocrinology, Jingzhou First People's Hospital, Yangtze University, 8 Hang-kong street, Jingzhou, Hubei 434000, People's Republic of China.
J Endocrinol Invest. 2013 May;36(5):298-302. doi: 10.3275/8525. Epub 2012 Jul 24.
Genetic variations in the engulfment and cell motility 1 (ELMO1) gene have recently been identified to be associated with nephropathy attributed to Type 2 diabetes mellitus (T2DM). Since T2DM-associated complications are proved to be more common among Asians than Western individuals, and Chinese people have a high incidence of diabetic nephropathy (DN), this study sought to analyze the association of ELMO1 gene polymorphisms with DN to probe into the effects of ELMO1 gene on susceptibility of DN in Chinese population.
We genotyped 6 polymorphism sites of ELMO1 gene in 200 unrelated Chinese subjects (123 T2DM with DN case subjects and 77 T2DM without DN control subjects). Genotyping was detected by a Sequenom MassARRAY genotyping system.
The strongest associations in ELMO1 gene with DN occurred at rs741301 [odds ratio (OR) 1.89; p=0.004] and rs10951509 (OR 1.76; p=0.02). Unconditional logistic regression analysis identified that the rs741301 polymorphism (presence of A allele, adjusted OR 3.27; p=0.03) and duration of T2DM (adjusted OR 1.15; p=0.04) were independent predictors for DN. The marker rs741301 located in intron 18 of ELMO1 gene was in strong linkage disequilibrium (LD) with rs11769038 (D'=0.91). Furthermore, haplotype analysis identified that haplotype 1 [CAAAGA] (OR 1.95; p=0.01), haplotype 2 [CAAAGG] (OR 0.50; p=0.01), and haplotype 9 [TGCGGG] (OR 0.17; p=0.007) of ELMO1 were significantly associated with DN.
This study first investigated the association of ELMO1 gene polymorphisms with DN in a Chinese population, supporting its key role as a candidate gene in the susceptibility of DN.
吞噬和细胞运动 1(ELMO1)基因的遗传变异最近被发现与 2 型糖尿病(T2DM)引起的肾病有关。由于 T2DM 相关并发症在亚洲人群中比西方人群更为常见,而中国人的糖尿病肾病(DN)发病率较高,因此本研究旨在分析 ELMO1 基因多态性与 DN 的关系,探讨 ELMO1 基因对中国人 DN 易感性的影响。
我们在 200 名无关的中国受试者中(123 例 T2DM 合并 DN 病例组和 77 例 T2DM 无 DN 对照组)检测了 ELMO1 基因的 6 个多态性位点。采用 Sequenom MassARRAY 基因分型系统进行基因分型。
ELMO1 基因与 DN 最强的关联发生在 rs741301[比值比(OR)1.89;p=0.004]和 rs10951509(OR 1.76;p=0.02)。条件 logistic 回归分析确定 rs741301 多态性(存在 A 等位基因,调整 OR 3.27;p=0.03)和 T2DM 病程(调整 OR 1.15;p=0.04)是 DN 的独立预测因子。位于 ELMO1 基因内含子 18 的标记 rs741301 与 rs11769038 高度连锁不平衡(D'=0.91)。此外,单体型分析确定 ELMO1 的单体型 1[CAAAGA](OR 1.95;p=0.01)、单体型 2[CAAAGG](OR 0.50;p=0.01)和单体型 9[TGCGGG](OR 0.17;p=0.007)与 DN 显著相关。
本研究首次在中国人群中研究了 ELMO1 基因多态性与 DN 的关系,支持其作为 DN 易感性候选基因的关键作用。