Endothelial Nitric Oxide Synthase Polymorphisms and Haplotypes in Amerindians

Abstract

Interethnic disparities in the distribution of endothelial nitric oxide synthase (eNOS) polymorphisms may affect nitric oxide (NO)-mediated effects of and responses to drugs. While there are differences between black and white subjects there is no information regarding the distribution of eNOS gene alleles and haplotypes in Amerindians. We studied three clinically relevant eNOS polymorphisms (T(-786)C in the promoter, a variable number of tandem repeats in intron 4, and the Glu298Asp in exon 7) and eNOS haplotypes in 170 Amerindians from three tribes of the Brazilian Amazon. The results were compared with previous findings for black and white Brazilians. The Asp298, C(-786), and 4a alleles were much less common in Amerindians (5.0%, 3.2%, and 4.1%, respectively) than in blacks (15.1%, 19.5%, and 32.0%, respectively) or whites (32.8%, 41.9%, and 17.9%, respectively) (p < 0.001). The haplotype including the most common alleles for each polymorphism was much more common in Amerindians (89%) than in blacks (45%) or whites (41%). Our findings are consistent with a lower genetic diversity in Amerindians compared with blacks and whites. These striking differences may be of major relevance for case-control association studies focusing on eNOS gene polymorphisms and may explain, at least in part, differences in the responses to cardiovascular drugs.

Endothelial Nitric Oxide Synthase Gene Polymorphisms (G894T, 4b/a and T-786C) and Preeclampsia: Meta-Analysis of 18 Case–Control Studies

“…Although individual eNOS polymorphisms apparently have minor effects on endogenous NO formation in healthy individuals, eNOS haplotypes combining three eNOS gene variants were shown to modulate NO formation (Metzger et al, , 2007Nagassaki et al, 2005;Barbosa et al, 2006;Sandrim et al, 2007). Interestingly, consistent interethnic differences in the distribution of eNOS genotypes and haplotypes have been reported (Tanus-Santos et al, 2001;Marroni et al, 2005;Luizon et al, 2009). These differences suggest a proportional significance of these polymorphisms in each ethnic group and may explain, in part, the ethnic disparities in preeclampsia risk.…”

Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

“…Genotypes for T-786C and Glu298Asp polymorphisms were determined by Taqman Allele Discrimination assay on Chromo 4 Detector (Bio-Rad Laboratories, USA) as previously described (Luizon et al, 2009). …”

The 27-bp VNTR Polymorphism in Intron 4 of the Human eNOS Gene in Healthy Singaporean Chinese, Indians, and Malays

“…The highest frequencies of genotypes 4/4 (15.0%) and 4/5 (39.0%) were detected in African Americans (Yanamandra et al 2005) and in black Brazilians (Luizon et al 2009). Singaporean Chinese had a higher frequency of genotype 4/5 (17.9%) than the Han Chinese from Northern China (12.9 and 16.5%) and Taiwan (14.3%).…”

“…Allele 2 was detected in African Americans (Tanus-Santos et al 2001) and in patients with myocardial infarction and venous thromboembolism (Hooper et al 1999). Allele 6 was also found at very low frequencies in 0.3% (Nishio et al 2005) or 0.9% (Droma et al 2002) of Japanese, 0.2% of Italians (Bolli et al 2007), and 0.7% of black Brazilians (Luizon et al 2009). In African Americans, however, the frequencies of allele 6 were much higher, ranging between 1.7 and 6.2% (Hooper et al 1999;Li et al 2004;Yanamandra et al 2005).…”