ACACβ gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes

Abstract

Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin-angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene-gene interaction between acetyl-coenzymeA carboxylase beta (ACACβ) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier. The present study was designed with the aim to examine the association of an ACACβ (rs2268388) and AGTR1 (rs5186) gene polymorphism with the risk of DN in Asian Indians. 1,158 patients with T2DM belonging to two independently ascertained North Indian and one South Indian cohorts were genotyped for ACACβ (rs2268388) and AGTR1 (rs5186) polymorphism using real time PCR-based Taq-man assay and PCR-RFLP assays. In all the three cohorts, a significantly higher frequency of T allele and TT genotypes of ACACβ and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACACβ and C allele of AGTR1 were found to be significantly associated with proteinuria, a hallmark of DN. We also found significant epistatic interactions between these two genes. TT genotypes of ACACβ gene and CC genotype of AGTR1 gene confers the risk of DN and both genes had significant epistatic interaction in Asian Indian patients with T2DM.

The association between lipid metabolism gene polymorphisms and nephropathy in type 2 diabetes: a meta-analysis

“…Ten studies reported on microalbuminuria [10,12,14,19,21,22,35,37,40,41], seven reported on macroalbuminuria [6,14,17,19,21,37,41], whereas only three studies were about ESRD [25]. Examining genotype frequencies in the controls, significant deviation from HWE was detected in the four studies [3,4,33,34]. All the studies we included gained score of 6-8 based on the Newcastle-Ottawa scale.…”

The Susceptibility Genes in Diabetic Nephropathy

“…A single nucleotide polymorphism (SNP) in intron 18 of ACACB that was identified by a large-sample meta-analysis in Japanese individuals (rs2268388) showed a significant association with type 2 diabetes-related nephropathy (T2DN). Researchers have found the strongest associations in Asian [9], including Chinese [8], and Caucasian populations by case-control studies [8, 9]. In a recent meta-analysis, Li et al [10] concluded that the T allele increases the susceptibility to T2DN.…”

“…Subsequently, a study of 3,561 Caucasian patients with T1DM revealed that the risk of developing DN increased significantly in AA genotype carriers [73]. The correlation was verified in different ethnic groups, such as Asians and Caucasians [9, 72]. However, Currie et al [74] found that the genotype and frequency of AGTR1 in 1467 Caucasian patients with T1DM were not related to DN.…”

TheACACBgene rs2268388 polymorphism is associated with nephropathy in Caucasian patients with diabetes: a meta-analysis

“…Data were found in three articles, 4,6,14 representing 11 studies (Table 1). Nine of the studies were case-control studies, 4,6 and two of them were cohort studies.…”