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Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population.

ABSTRACT: Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease, characterized by progressive albuminuria and conferring additional risk of cardiovascular disease (CVD) and mortality. The crucial role of heat-shock proteins (HSPs) on renal function in patients with DN has been well documented. The present study was aimed to understand the association of HSP-70 gene variants on the susceptibility of Type 2 Diabetes Mellitus (T2DM) and DN. A total of 946 subjects (549 Males; 397 Females) were recruited and divided into four groups according to the levels of urinary albumin excretion (UAE): those with normoalbuminuria (UAE <30 mg/24 h; n=230), those with microalbuminuria (30? UAE ?300 mg/24 h; n=230), and those with macroalbuminuria (UAE> 300 mg/24 h; n=230). The control group randomly enrolled a consecutive population of 256 healthy subjects who had a routine medical check-up in our hospital. Those subjects had no history or clinical symptoms of diabetes. Subjects were genotyped for HSP70-2 (+1538 A/G; rs2763979) and HSP70-hom (+2437 C/T; rs2227956) by PCR-restriction fragment length polymorphism (RFLP). The 'G' allele of HSP70-2 (+1538 A/G) single nucleotide polymorphism (SNP) showed relative risk for normoalbuminuria, microalbuminuria and macroalbuminuria subjects whereas the 'T' allele of HSP70-hom (+2437 C/T) SNP showed significant protection against macroalbuminuria subjects. In conclusion, our results indicate that the HSP70-2 (+1538 A/G) and HSP70-hom (+2437 C/T) SNPs are highly associated with renal complications in T2DM among the South Indian population.

SUBMITTER: Dhamodharan U

PROVIDER: S-EPMC5469327 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population.

Dhamodharan Umapathy U Ezhilarasi Krishnamoorthy K Ponjayanthi Balashanmugam B Sireesh Dornadula D Ramkumar Kunka Mohanram KM Viswanathan Vijay V

Bioscience reports 20170327 2

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease, characterized by progressive albuminuria and conferring additional risk of cardiovascular disease (CVD) and mortality. The crucial role of heat-shock proteins (HSPs) on renal function in patients with DN has been well documented. The present study was aimed to understand the association of <i>HSP-70</i> gene variants on the susceptibility of Type 2 Diabetes Mellitus (T2DM) and DN. A total of 946 subjects (549 Males; 397 F ...[more]

PMID: 28246355

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Project description:PURPOSE: Primary angle closure (PAC) is the early stage of primary angle closure glaucoma (PACG). It is believed that the formation of PAC is regulated by a tissue remodeling pathway. This study investigated the association between gene variants in extracellular matrix metalloprotease-9 (MMP-9), methylenetetrahydrofolate reductase (MTHFR), frizzled-related protein (MFRP), heat shock protein 70 (HSP70), and PAC. METHODS: The study was part of the Jiangsu Eye Study. The sample consisted of 232 subjects with PAC and 306 controls obtained from a population-based prevalence survey conducted in Funing County in Jiangsu Province, China. The single nucleotide polymorphisms (SNPs) included rs17576 and rs3918249 in MMP-9, rs1801133 in MTHFR, rs3814762 in MFRP, and rs1043618 in HSP70. SNP genotyping was performed with a TaqMan MGB probe using the real-time PCR system. RESULTS: Among the five SNPs tested, only MFRP rs3814762 and HSP70 rs1043618 showed a nominal association with PAC. The frequency of the minor T allele of MFRP rs3814762 was higher in the control group than in the PAC group (uncorrected p=0.016 and p=0.027, for alleles and genotypes, respectively) and conferred an odds ratio (OR) of 0.67 in the allelic analysis, indicating a protective role of the SNP in developing PAC. In contrast, the frequency of the CC genotype of HSP70 rs1043618 was higher in the PAC group than in the control group (uncorrected p=0.048 and p=0.022 for the genotypes general model and recessive model, respectively) and conferred an OR of 1.79 in the recessive model, indicating a harmful role in developing PAC. However, the differences did not remain statistically significant after Bonferroni correction. The remaining three SNPs showed no differences in the distribution of the genotypes and allele frequencies between the two groups. CONCLUSIONS: Our study reveals a suggestive association of MFRP and HSP70 with PAC in a Han Chinese population. The results from this population-based survey will serve as the baseline for prospective observation of the role of tissue remodeling pathway in the development of PACG.

Dataset Information

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population.

Publications

Association of A1538G and C2437T single nucleotide polymorphisms in heat shock protein-70 genes with diabetic nephropathy among South Indian population.

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