Distribution of Endothelial Nitric Oxide Synthase Gene Polymorphisms in Turkish Population

Abstract

Nitric oxide (NO) is the major mediator in the regulation of vascular homeostasis. It is synthesized by endothelium from arginine with the catalytic help of endothelial NO synthase (eNOS). Polymorphisms in the eNOS gene have been associated inconsistently with many vascular diseases. Conflicting results may arise from ethnic variations, notably in control-case studies. Therefore, to obtain reliable information and improve the design of such genetic association studies, we examined the distribution of genetic alleles of 3 clinically relevant eNOS polymorphisms (the variable number of tandem 27-base pair [bp] repeats in intron 4, T-786C in promoter, and G894T in exon 7) in 300 healthy Turkish individuals with a mean age of 50.07 (SD 12.15) years (range, 22-78 years; 50.7% men and 49.3% women). The haplotype frequency was estimated and associations between 3 polymorphisms were evaluated. We discussed the similarity and differences in the distribution of alleles with other populations. The allele frequencies were 45.3%, 48%, and 62.7% for GG of exon 7, TT of promoter, and bb of intron 4 (wild types), respectively. The most common haplotype combines the wild-type alleles (G-T-b) for all 3 polymorphisms (estimated frequency, 37.6%). The linkage analysis between each pairwise combination showed specific associations between T-786C polymorphism in promotor and G894T polymorphism in exon 7 (positive D' value, +0.3387). No significant correlation was found in the genotype distribution of the 3 polymorphisms with age, sex, and obesity. Our eNOS gene allele distributions resemble those of Caucasians and white populations. Our data showed ethnic differences with other populations in the allele distribution of eNOS gene besides conserved distribution of these polymorphisms in Turkish population. This study produced a reference control data for the 3 eNOS polymorphisms in Turkish population and will be helpful in planning eNOS association studies in vascular disease.

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

“…Of note, we and others had previously reported that there was no deviation in T/G allele frequencies from the Hardy-Weinberg equilibrium in the HF patient group compared to the healthy control group, genotype frequencies reported in the Single Nucleotide Polymorphism Database (dbSNP), or other ethnic groups [34,40].…”

Polymorphism of the gene eNOS G894T (Glu298Asp) in symptomatic patients with aterosclerosis

“…However, when the relationship between the G894T polymorphism of the eNOS gene between the case and control groups with both male and female genotypes was evaluated in our study, no statistical difference was found. Sinici et al (2009) investigated G894T polymorphism in the Turkish population and its correlation with vascular disease and also did not find a significant correlation between male and female. Gad et al (2012) also found no statistical difference between male and female that could contribute to a greater influence on the polymorphism on the Egyptian population.…”

Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

“…Importantly, marked differences in both genotype and haplotype frequencies of NOS3 exist between ethnicities, which could explain some of the discrepancies between studies. 26,28 The etiology behind the sex differences in SAH patients remains unknown. Earlier studies indicate that women have higher blood flow velocities, especially in the posterior circulation, and that autoregulation of cerebral blood flow may function differently in men and women under some circumstances such as orthostatic stress.…”