Interaction of G-protein 3 Subunit and Nitric Oxide Synthase Gene Polymorphisms on Carotid Artery Intima-media Thickness in Young Adults: The Bogalusa Heart Study

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BACKGROUND: G-protein beta3 subunit (GNB3) gene C825T and endothelial nitric oxide (eNOS) gene G894T polymorphisms both influence arterial structure and function. However, information is scant regarding the interaction of these genes on arterial wall thickness. METHODS: This aspect was examined in 654 white and black subjects, aged 25-43 years (72.9% white, 39.3% male). Arterial wall thickness was assessed in terms of the average intima-media thickness (IMT) of common carotid, internal carotid, and carotid bulb segments by B-mode ultrasonography. RESULTS: Frequencies of T allele of the GNB3 C825T polymorphism (0.718 vs. 0.304, P < 0.0001) and G allele of the eNOS G894T polymorphism (0.868 vs. 0.661, P < 0.0001) were higher in blacks compared to whites. In a multivariate model including gender, age, mean arterial pressure, body mass index, triglycerides/HDL cholesterol ratio, insulin resistance index, smoking, and/or race, there was no significant genotypic effect on carotid IMT with respect to GNB3 C825T or eNOS G894T polymorphisms among whites, blacks, and total sample. However, the carriers of TT genotype of the GNB3 C825T and T allele of the eNOS G894T had a significantly lower carotid IMT among blacks (P = 0.003) and the total sample (P = 0.006). CONCLUSION: These results indicate that the genetic variations of the eNOS gene in combination with the GNB3 gene jointly influence carotid artery wall thickening process in young adults, especially in blacks.

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