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BMC Medical Genetics

, 15:9

First Online: 16 January 2014Received: 25 July 2012Accepted: 06 January 2014

Abstract

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 31, 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.

AbbreviationsADAThe American Diabetes Association

ASNThe American Society of Nephrology

DMDiabetes mellitus

DNDiabetic nephropathy

EASDThe European Association for the Study of Diabetes

eNOSEndothelial nitric oxide synthase

ESRDEnd stage renal disease

GFRGlomerular filtration rate

iNOSInducible nitric oxide synthase

NKAThe National Kidney Association

nNOSNeuronal nitric oxide synthase

NONitric oxide

NOSNitric oxide synthase

PRISMAThe preferred reporting items for systematic reviews and meta-analysis

SNPSingle nucleotide polymorphism.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-15-9 contains supplementary material, which is available to authorized users.

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Autor: Bruno Schmidt Dellamea - Lana Catani Ferreira Pinto - Cristiane Bauermann Leitão - Katia Gonçalves Santos - Luis Henri

Fuente: https://link.springer.com/







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