Endothelial nitric oxide synthase polymorphisms and haplotypes in Amerindians.
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.
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Marcelo R
MR
Luizon
Tatiane C
TC
Izidoro-Toledo
Aguinaldo L
AL
Simoes
Jose E
JE
Tanus-Santos
D044383:Black People / Q000235:genetics; D001938:Brazil / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D007438:Introns / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D020080:Tandem Repeat Sequences / Q000235:genetics; D044465:White People / Q000235:genetics
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III