A genome-wide association study for diabetic nephropathy genes in African Americans

Abstract

A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.

Non-Muscle Myosin Heavy Chain 9 Gene (MYH9) Polymorphism (rs4821481) is Associated with Urinary Albumin Excretion in Iranian Diabetic Patients

“…Effects of MYH9 polymorphism on renal function in healthy European subjects, but not in diabetic patients, have been suggested (27). Although various reports have displayed associations between MYH9 polymorphism and non-diabetic ESRD, there are controversial reports about the presence of MYH9 polymorphism in diabetic ESRD (5,(28)(29)(30). Most of the reports have not demonstrated a significant association between MYH9 polymorphism and diabetic ESRD (18,28,29).…”

“…Managing every aspect of chronic kidney disease is one of the greatest challenges that healthcare systems have ever confronted (1)(2)(3), and its devastating aftermath may result in earlier morbidities and higher mortality rates. However, this can be monitored and prevented with appropriate insight into the disease, which would lead to less financial pressure on healthcare systems and better care for patients suffering from chronic diseases (4)(5)(6). Despite the multifactorial nature of DN, genetic factors have always been considered to be involved in the inheritance and development of disease.…”

Intracranial aneurysm risk factor genes: relationship with intracranial aneurysm risk in a Chinese Han population

“…The KCNJ15 gene, encoding a potassium channel, was associated with obese T2DM, and genetic variants of KCNJ15 have been shown to reduce insulin secretion (Fukuda et al, 2013). The SFI1 gene, encoding a homolog of the yeast suppressor of the cAMP pathway/spindle assembly protein, has been associated with diabetic nephropathy (McDonough et al, 2011).…”

Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes

“…aspx, accessed 08/08/2012) [28]. Notably, in a GWAS for DN in African-Americans, another variant (rs2358944), located 57 kb downstream of the HMGA2 rs1531343, was one of the strongest signals associated with diabetic ESRD, but also to a lesser extent with non-diabetic ESRD [29].…”