Endothelial nitric oxide synthase gene haplotypes affect nitrite levels in black subjects

Abstract

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated with variations in nitric oxide (NO) formation and response to drugs in white subjects. We examined whether genetic polymorphisms (T-786C, b/a intron 4 and Glu298Asp) and haplotypes of the eNOS gene affect NO formation in 179 healthy black subjects. To assess NO formation, we measured the concentrations of nitrite in the plasma, red blood cells and whole blood. Although we found no effects of individual eNOS polymorphisms on NO formation, we found that the 'C-4b-Glu' haplotype is significantly more common in subjects with low circulating plasma and whole blood nitrite concentrations compared with subjects with high circulating nitrite concentrations (both P<0.0007). These findings reproduce previous findings in white subjects and are consistent with the idea that defining genetic markers is more important than ethnic classification, at least in terms of NO formation.

Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome

“…In a study conducted with healthy men, no significant association was found between eNOS genotypes and NO levels, whereas a significant increase was found in the frequency of alleles C (promoter), 4b (intron 4), and Glu (exon 7) in the group with low NO levels [20]. However, in healthy African-American subjects, it was found that T-786C and Glu298Asp polymorphisms did not affect production of NO, although the frequency of the “C-4b-Glu” haplotype was significantly increased in patients with low NO levels [21]. Tsukada et al found that plasma NO levels of subjects who are homozygous for the a allele were nearly 20% lower than those in subjects with the b allele [22].…”

Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients

“…Research studies in humans have suggested that several eNOS gene variants combined within a specific haplotype may have a more significant effect on NO modulation than individual eNOS polymorphisms [43,44]. In addition, polymorphisms that represent the information of neighboring single-nucleotide polymorphisms in linkage disequilibrium may affect endogenous NO formation, and were shown to be associated with low circulating whole blood nitrite concentrations, indicating low levels of NO production [45].…”

Association between endothelial NO synthase polymorphisms and arterial properties in the general population

“…The bioavailability of NO in the arterial wall also depends on other factors such as the presence of substrate and co-factors for eNOS, the phosphorylation status of eNOS, and the presence of reactive oxygen species which can inactivate NO. It was shown that NO production and consequently blood nitrite levels, marker of endogenous nitric oxide production, might be affected by rs3918226 polymorphism alone [21] or by NOS3 haplotypes including other two SNPs under study [10,27,28]. We and others [22,29,30] observed that the three studied genotypes are in high linkage disequilibrium (in our hands the Lewontin's D was ≥0.95).…”