Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians

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• 作者：Hela Ben Nasr^a ; Saloua Dimassi^a ; Refka M&rsquo ; hadhbi^a ; Haithem Debbabi^a ; Mondher Kortas^b ; Zouhair Tabka^a ; Karim Chahed^a ; ^c ; ^{k.chahed@yahoo.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NOS3 ; G894T polymorphism ; VNTR 4a/b variant ; Body mass index ; Obesity
• 刊名：Obesity Research & Clinical Practice
• 出版年：2016
• 出版时间：July-August 2016
• 年：2016
• 卷：10
• 期：4
• 页码：465-475
• 全文大小：879 K

文摘

The endothelial nitric oxide synthase (NOS3) has been shown to play a role in the modulation of lipolysis. The goal of this study was to examine the impact of the G894T (rs1799983) and a 27 bp variable number of tandem repeats (VNTR 4a/b) of NOS3 gene on obesity in a sample of the Tunisian population.

Research methods and procedures

The study included 211 normal weight subjects and 183 obese patients. NOS3 G894T and 4a/b variants were determined by PCR analysis and examined for association with obesity-related traits. The effect of obesity on forearm skin blood flow (FSBF) response to acetylcholine, an endothelium-dependent vasodilator was determined by laser Doppler iontophoresis.

Results

In case–control studies, both G894T and 4a/b variants were associated with obesity. A significantly increased risk of obesity was found with the NOS3(G894T) TT genotype (OR:2.62, P = 0.04). This association remains significant after adjustments for age and gender (OR: 2.93, P = 0.03). A higher risk was also observed for carriers of the G894T allele (OR: 1.72, P = 0.001). Stratified analysis by gender revealed that obese men (but not women) had significantly higher frequency of TT genotypes compared to controls (9.9% vs. 2.9%, P = 0.01). Carriers of the 4b allele presented a significantly higher risk of obesity than non-carriers even after adjustments for age and gender (OR (95%CI): 1.72 (1.16–2.56), P = 0.004). Correlations with anthropometric parameters revealed that carriers of TT and bb genotypes had significantly higher body mass index compared to those homozygous for the G and a alleles (P = 0.0004).

Conclusion

This study provides the first evidence for the association of G894T and 4a/b variants with body mass index and the risk of obesity in Tunisians. These polymorphisms did not exhibit, however any significant association with both metabolic traits and vascular function.