Mehrabzadeh Mohsen, Pasalar Parvin, Karimi Mostafa, Abdollahi Maryam, Daneshpour Maryam, Asadolahpour Effat, Razi Farideh
Department of Medical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Science Institute, Tehran University of Medical Sciences, Tehran, Iran.
J Diabetes Metab Disord. 2016 Oct 7;15:43. doi: 10.1186/s40200-016-0265-3. eCollection 2015.
Diabetic nephropathy (DN) is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM). Several genome-wide association studies have introduced Engulfment and Cell Motility 1 (ELMO1) as a candidate gene which is associated with DN. This study assessed the association of ELMO1 gene polymorphisms with DN in order to investigate the effects of ELMO1 gene on susceptibility to DN in an Iranian population.
In the present study, 100 patients with T2DM, 100 patients with DN and 100 healthy subjects who were matched for sex were selected. Allele and genotype frequencies were determined by Tetra-ARMS PCR technique. In all groups, levels of FBS, creatinine, urea, HbA1C, urine levels of albumin creatinine ratio and glomerular filtration rate were measured.
A statistically significant association was shown between G allele of rs741301 (odds ratio (OR) = 1.7 [95 % CI 1.17-2.63]; value = 0.005), and GG genotypes of rs741301 (OR = 2.5 [95 % CI 1.2-5.4]; value = 0.01) and DN. A significant association was not detected between allelic and genotypic frequencies of rs1345365 and DN. Linkage Disequilibrium (LD) between two variants was weak (D' = 0.11, r2 = 0.008). rs1345365A/rs741301A haplotypes were more frequent in patients with T2DM as compared to DN (OR = 0.5 [95 % CI 0.3-0.7]; value = 0.0006). Also, genotypes of variant rs741301 in all subjects had significant difference with respect to the mean of ACR ( Value < 0.05).
This study first investigated the association of ELMO1 gene polymorphisms (rs741301) with DN in an Iranian population, supporting its key role as a candidate gene in the susceptibility to DN.
糖尿病肾病(DN)是2型糖尿病(T2DM)患者的主要死亡原因之一。多项全基因组关联研究已将吞噬与细胞运动蛋白1(ELMO1)作为与DN相关的候选基因。本研究评估ELMO1基因多态性与DN的关联,以探讨ELMO1基因对伊朗人群DN易感性的影响。
在本研究中,选取了100例T2DM患者、100例DN患者和100例性别匹配的健康受试者。采用四引物扩增受阻突变系统聚合酶链反应(Tetra-ARMS PCR)技术测定等位基因和基因型频率。在所有组中,测量空腹血糖(FBS)、肌酐、尿素、糖化血红蛋白(HbA1C)、尿白蛋白肌酐比值和肾小球滤过率水平。
rs741301的G等位基因(比值比(OR)=1.7 [95%置信区间1.17 - 2.63];P值=0.005)以及rs741301的GG基因型(OR = 2.5 [95%置信区间1.2 - 5.4];P值=0.01)与DN之间存在统计学显著关联。未检测到rs1345365的等位基因和基因型频率与DN之间存在显著关联。两个变体之间的连锁不平衡(LD)较弱(D' = 0.11,r2 = 0.008)。与DN相比,rs1345365A/rs741301A单倍型在T2DM患者中更常见(OR = 0.5 [9,5%置信区间0.3 - 0.7];P值=0.0006)。此外,所有受试者中rs741301变体的基因型在尿白蛋白肌酐比值(ACR)平均值方面存在显著差异(P值<0.05)。
本研究首次在伊朗人群中调查了ELMO1基因多态性(rs741301)与DN的关联,支持其作为DN易感性候选基因的关键作用。