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Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis.

ABSTRACT: A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus (DM) patients. Nevertheless, the results are inconclusive and inconsistent.We screened PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Wanfang databases for those relevant studies updated in May 2016.7 studies involving 2564 subjects were recruited. We evaluated the genotypic and allelic differences between DN patients and DM controls. Overall analysis showed that no significant association was found among the ApaI, BsmI, FokI,TaqI gene polymorphisms and DN susceptibility in diabetic patients (all P values > 0.05). In the stratified analysis, TT genotype was related to DN susceptibility in Asians (TT vs Tt + tt: OR =2.21, 95% CI: 1.05-4.67, p = 0.04). The sensitivity analysis showed that the results in overall populations, Caucasians and Asians were dependable.No significant association was found among the ApaI, BsmI, FokI, TaqI polymorphisms and DN risk in overall populations, the TaqI variants might related to DN susceptibility in Asians. Further researches are required to testify our meta-analysis.

SUBMITTER: Yang L

PROVIDER: S-EPMC5575903 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis.

Yang Lina L Wu Lan L Fan Yi Y Ma Jianfei J

BMC medical genetics 20170829 1

<h4>Background</h4>A large amount of researches have demonstrated that vitamin D receptor (VDR) gene polymorphisms are associated with diabetic nephropathy (DN) risk in diabetes mellitus (DM) patients. Nevertheless, the results are inconclusive and inconsistent.<h4>Methods</h4>We screened PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Wanfang databases for those relevant studies updated in May 2016.<h4>Results</h4>7 studies involving 2564 subjects were recruited. We evalua ...[more]

PMID: 28851298

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Project description:BACKGROUND:Diabetic nephropathy (DN) is a multifactorial disease with gene-environment interaction resulting in progressive renal function damage. Multiple studies have assessed the association between matrix metalloproteinase-9 (MMP-9) gene promoter polymorphism and DN susceptibility. However, the results are inconclusive. In the present study, we will conduct a meta-analysis to further examine this relationship more precisely. METHODS:Electronic databases (Pubmed, Web of Science, Embase, Google Scholar, Wanfang, China Biological Medicine and China National Knowledge Infrastructure) will be used to search clinical case-control studies about MMP-9 polymorphism and DN published until 18 August 2020. The language will be restricted to Chinese and English. Two reviewers will take charge of completing the selection of study, the extraction of data as well as the assessment of study quality independently. The Newcastle-Ottawa Scale will be used to evaluate the study quality. We will evaluate the association under 5 genetic models. Fixed-effects or random-effects models will be used to calculate the effect sizes of odds ratio and 95% confidence intervals. Afterwards, subgroup analysis will be conducted in terms of the ethnicity and genotyping method. Additionally, sensitivity analysis will be performed via sequentially omitting each of the included studies one at a time. The funnel plots, Egger regression test, and Begg rank correlation test will be used to test the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0. RESULTS:This protocol reported according to the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. This study will provide a better understanding of the association between MMP-9 polymorphisms and DN risk. CONCLUSION:Publishing this protocol will minimize the potential bias related to data mining, thus contributing to generation of reliable evidence. OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/H5FS4.

Project description:BackgroundNitric oxide (NO) has numerous functions in the kidney, including control of renal and glomerular hemodynamics, by interfering at multiple pathological and physiologically critical steps of nephron function. Endothelial NOS (eNOS) gene has been considered a potential candidate gene to diabetic nephropathy (DN) susceptibility. Endothelial nitric oxide synthase gene (eNOS-3) polymorphisms have been associated with DN, however some studies do not confirm this association. The analyzed polymorphisms were 4b/4a, T-786C, and G986T.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used in this report. Case-control studies that had diabetic patients with DN as cases and diabetic patients without nephropathy as controls, as well as that evaluated at least one of the three polymorphisms of interest were considered eligible. All studies published up until December 31st, 2012 were identified by searching electronic databases. Hardy-Weinberg equilibrium assessment was performed. Gene-disease association was measured using odds ratio estimation based on the following genetic contrast/models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model.ResultsTwenty-two studies were eligible for meta-analysis (4b/a: 15 studies, T-786C: 5 studies, and G984T: 12 studies). Considering 4b/a polymorphism, an association with DN was observed for all genetic models: allele contrast (OR = 1.14, CI: 1.04-1.25); additive (OR = 1.77, CI: 1.37-2.28); recessive (OR = 1.77, CI: 1.38-2,27); dominant (OR = 1.12, CI: 1.01-1.24), with the exception for co-dominance model. As well, T-786C polymorphism showed association with all models, with exception for co-dominance model: allele contrast (OR = 1.22, CI: 1.07-1.39), additive (OR = 1.52, CI: 1.18-1.97), recessive (OR = 1.50, CI: 1.16-1.93), and dominant (OR = 1.11, CI: 1.01-1.23). For the G894T polymorphism, an association with DN was observed in allelic contrast (OR = 1.12, CI: 1.03-1.25) and co-dominance models (OR = 1.13, CI: 1.04-1.37).ConclusionsIn the present study, there was association of DN with eNOS 4b/a and T-786C polymorphism, which held in all genetic models tested, except for co-dominance model. G894T polymorphism was associated with DN only in allele contrast and in co-dominance model. This data suggested that the eNOS gene could play a role in the development of DN.

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Dataset Information

Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis.

Publications

Vitamin D receptor gene polymorphisms in association with diabetic nephropathy: a systematic review and meta-analysis.

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