Effect of polymorphism of the endothelial nitric oxide synthase and apolipoprotein E genes on carotid atherosclerosis in hemodialysis patients.

Background: Decreased synthesis of nitric oxide (NO) and dyslipidemia are implicated in the development of atherosclerosis.

Methods: We investigated the relationship between endothelial NO synthase (eNOS) gene polymorphism, apolipoprotein E (apoE) polymorphism, and carotid atherosclerosis in 163 hemodialysis patients with nondiabetic nephropathy. Intima media thickness of the carotid artery was measured by ultrasonography, and subjects were classified according to the presence or absence of carotid plaque. Multivariate odds ratios were calculated to assess the combined influence of several variables on the existence of carotid plaque, with clinical factors, the intron 4 polymorphism, T(-786)-->C polymorphism, and Glu298Asp polymorphism of eNOS and the apoE polymorphism tested as independent predictors. We also investigated the combined effect of these polymorphisms on risk for plaque.

Results: The odds ratio for carotid plaque positivity was increased to 3.72 by the a allele of the intron 4 polymorphism and increased to 3.36 by the C allele of the T(-786)-->C polymorphism, but was not increased in subjects with the T allele of the Glu298Asp polymorphism or those with the epsilon4 allele of the apoE polymorphism. However, the odds ratio for plaque positivity was significantly increased to 4.00 by possession of the a allele and/or epsilon4 allele and also increased to 4.04 by the C allele and/or epsilon4 allele.

Conclusion: This cross-sectional study showed a synergistic effect between the intron 4 polymorphism or T(-786)-->C polymorphism of the eNOS gene and the apoE polymorphism with respect to risk for carotid atherosclerosis in nondiabetic hemodialysis patients.