Abstract
BackgroundDiabetic 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.MethodsIn 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.ResultsA statistically significant association was shown between G allele of rs741301 (odds ratio (OR) = 1.7 [95 % CI 1.17–2.63]; p value = 0.005), and GG genotypes of rs741301 (OR = 2.5 [95 % CI 1.2–5.4]; p 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]; p value = 0.0006). Also, genotypes of variant rs741301 in all subjects had significant difference with respect to the mean of ACR (p Value < 0.05).ConclusionThis 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.
Highlights
Diabetic nephropathy (DN) is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM)
Study subjects This case–control study was performed between January and December 2015 in the Diabetes and Metabolic research Center affiliated to Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences (TUMS), Tehran, Iran
Systolic blood pressure, body mass index (BMI), duration of diabetes, fasting blood sugar, HbA1C, serum creatinine, serum urea, and albumin/creatinine ratio (ACR) were higher in DN group compared to Type diabetic without Nephropathy (DM) and healthy controls (HC) groups
Summary
Diabetic nephropathy (DN) is one of the leading causes of death in patients with type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) has become a silent pandemic over the past few decades, resulting in remarkable loss in government’s economy, and has endangered human health [1, 2]. The most important risk factors such as hyperglycemia, hypertension, diabetic duration, hyperlipidemia, chronic inflammation, familial clustering and genetic determinants can Mehrabzadeh et al Journal of Diabetes & Metabolic Disorders (2016) 15:43 make a diabetic patient susceptible to DN. Main part of the research on DN evaluates the genetic role in DN pathogenesis because elucidation of genes associated with DN can help for better understanding of disease molecular mechanism, complications, prevention and treatment [12]. Early identification and more severe therapies can reduce the outcome of DN
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