Association between 894G>T endothelial nitric oxide synthase gene polymorphisms and metabolic syndrome

Abstract

Metabolic syndrome (MS) is a cluster of cardiovascular risk factors such as hypertension, dyslipidemia, obesity and type II diabetes. Here, we performed a case-control study analyzing the association between 894G>T endothelial nitric oxide synthase gene polymorphism (NOS3) and MS in 616 subjects. Genotype frequencies were TT= 9.3%, GG= 37.2 and TG= 53.6% and the allelic frequencies were T=0.36 and G= 0.64. We observed a higher TT genotype frequency in the male MS group than control subjects (p=0.02), independent of other variables. We found an association between hypertension and TT genotype in females. Our data suggests that 894G>T plays a signifi cant role in the mechanistic interaction between metabolic risk such as hypertension and MS, although sex-related differences may exist. A síndrome metabólica (SM) é um agrupamento de fatores de riscos cardiovasculares, tais como hipertensão, dislipidemia, obesidade e diabetes tipo 2. Realizou-se um estudo caso-controle para analisar a associação entre o polimorfi smo (894G>T do gene da enzima endotelial oxido nítrico sintetase (NOS3) e a SM em 616 voluntários. As freqüências genotípicas foram: TT = 9,3%, GG = 37,2% e TG = 53,6%, e as freqüências alélicas T = 0,36 e G = 0,64. Observou-se freqüência mais alta do genótipo TT em homens com SM do que nos controles, independentemente de outros fatores (p = 0,02). Também observou-se associação entre hipertensão e o genótipo TT nas mulheres. Os dados do estudo sugerem que o polimorfi smo 894G>T pode ter papel significativo na interação entre riscos metabólicos, tais como a hipertensão e a SM, ainda que existam diferenças relacionadas ao sexo.

Variants of endothelial nitric oxide synthase gene are associated with components of metabolic syndrome in an Arab population

“…Similarly, the 894G>T SNP, albeit in a haplotypic association with other SNPs, is linked to the features of MetS [21]. In our study, genotype distribution of 894G>T SNP was not associated with MetS which was in agreement with pervious study in Caucasian [25] but not with data from Chinese [22] and Brazilian [24] populations. This inconsistency could possibly be due to the difference in genetic background and sample was in weak linkage disequilibrium with -786T>C (R 2 =0.182, D' = 0.2357; p <0.001).…”

“…In a Chinese population the GT+TT genotype of 894G>T SNP is significantly associated with total cholesterol, triglycerides and LDL-cholesterol [22], whereas the same genotype is a risk factor for HDL-and LDL-cholesterol and LDL particle size but not for total cholesterol and triglyceride in a Japanese population [23]. Likewise, the GT+TT genotype has been linked to dyslipidemia in Brazilian subjects with MetS [24], and to triglyceride levels in healthy African Americans [16]. In agreement with our result, the 4a/b polymorphism in Mexican Americans is associated with decreased HDL-cholesterol and the same polymorphism is associated decreased HDL-and increased LDL-cholesterol in Anglo-Celtic Caucasians [11,37].…”

“…Only very limited and contrasting informations are available on the possible association of 894G>T, 4a/b and -786T>C SNPs of eNOS gene with MetS, [20][21][22][23][24][25], and, in particular, no data are present in the literature on the likelihood that these genetic factors could play a role in the development of MetS in the Arab nations. These data are urgently needed considering that the incidence of MetS and its components is rising dramatically in many Arab countries including Saudi Arabia.…”

Association between Endothelial Nitric Oxide Synthase Polymorphisms and Risk of Metabolic Syndrome

“…Therefore, NOS3 might be a good candidate gene for evaluating MetS. Although evidence from epidemiological studies implied that the NOS3 gene was related to the pathogenesis of MetS, findings are inconsistent and controversial [25][26][27][28][29][30][31][32][33][34][35][36][37].…”

Disfunção endotelial no diabetes melito e estados de resistência à insulina: papel do estresse oxidativo e potenciais oportunidades terapêuticas

“…Sua presença é preditora de eventos cardiovasculares (2), surge nas fases iniciais da doença aterosclerótica e pode ser revertida por meio de medidas terapêuticas que sabidamente são capazes de reduzir a evolução dessa doença, tais como exercício físico, melhora da hiperglicemia do DM (3), cessação do fumo (4), uso de estatinas, entre outras. São mecanismos causais da disfunção endotelial nos estados de resistência à insulina e DM: alteração de vias de sinalização que levam à inativação da eNOS, ativação do endotélio por moléculas pró-inflamatórias, disfunção mitocondrial e aumento do estresse oxidativo na vasculatura (1), os quais podem ser particularmente importantes de acordo com fatores genéticos predisponentes (5). O estresse oxidativo é induzido pelas espécies reativas de oxigênio (EROs) e o ânion superóxido reage com o NO para formar peroxinitrito, substância altamente reativa.…”