Association betweenMYH9andAPOL1Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes in a Chinese Han Population

Abstract

Single-nucleotide polymorphisms (SNPs) in MYH9-APOL1 gene regions have been reported to be associated with diabetic kidney disease (DKD) in the American population. We examined the association between polymorphisms in MYH9-APOL1 and DKD susceptibility in a Chinese Han population. MYH9 rs3752462 (T>C) and APOL1 rs136161 (C>G) were genotyped in 303 DKD patients and 364 type 2 diabetes mellitus (T2DM) patients without kidney disease using the TaqMan SNP genotyping assay. Chi-squared test and multivariate logistic regression were used to evaluate the association. We observed that only MYH9 rs3752462 was associated with DKD (genotype, P = 0.004; allele, P = 0.002). Genetic model analysis revealed that rs3752462 was associated with increased risk of DKD under a dominant model adjusted by age and sex (adjusted odds ratio (aOR), 1.675; 95% CI 1.225–2.289; P = 0.001) and an additive model (TC versus TT: aOR, 1.649; 95% CI 1.187–2.290; CC versus TT: aOR, 1.817; 95% CI 0.980–3.367; P = 0.005). The combined effect of rs3752462 TC + rs136161 CC genotype showed an association of DKD adjusted by age and sex (aOR, 1.732; 95% CI 1.128–2.660; P = 0.012). After a Holm-Bonferroni correction for multiple tests, the C allele frequencies of the rs3752462 and the TC + CC genotype in the dominant model were considered statistically significant with a markedly increased risk of DKD (P < 0.00208; P < 0.002). Our results suggest that MYH9 rs3752462 is significantly associated with an increased risk of DKD in Chinese Han individuals.

Effect of donor non-muscle myosin heavy chain (MYH9) gene polymorphisms on clinically relevant kidney allograft dysfunction

“…As recently stated by Zhao et al, some studies on variants of interest in individuals suffering from diabetes or kidney disease point at vascular abnormalities as a pathology linking nephrogenic alleles with CKD [41]. Rs3752462 was found to correlate with cerebral blood flows in individuals with Diabetic Kidney Disease [42], blood pressure control in patients with CKD [16] and in our previous study with transplanted kidney artery stenosis [43], all those potentially being markers of vessel wall genetic preponderance to injury or dysfunctional healing.…”

The Association of UNC13B Gene Polymorphisms and Diabetic Kidney Disease in a Chinese Han Population

“…However, these associations fell short of statistical significance from those observed in French populations [6]. However, a limitation of previous studies was that most failed to investigate haplotype and disease correlation at the candidate gene locus [12,13]. These findings highlight that studies on the UNC13B gene in other populations with DKD is important as there may be different environmental and ethnic differences that are biologically relevant and involved in DKD in T2DM.…”

Association between PNPLA2 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in a Chinese Han Population with Type 2 Diabetes

“…Genotyping was confirmed by polymerase chain reaction (PCR) using the TaqMan SNP Genotyping Assay (Applied Biosystems, Waltham, MA, USA) and the ABI PRISM 7500 Sequence Detection System (Applied Biosystems). The amplification conditions were determined based on our previous research [ 14 ].…”

“…For SNP rs1138714 (A>G), G is the minor allele. The statistical analysis was carried out by following our previous research [ 14 ]. For all statistical tests of this study, statistical analysis was performed with SPSS software (version 20.0), and two-tailed P values less than 0.05 were considered statistically significant.…”