title: Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms.
abstract: A maldistribution of endothelial nitric oxide synthase (eNOS) genetic variants may explain differences in NO-mediated effects and response to drugs among black and white subjects. While interethnic differences in the distribution of eNOS genetic variants exist in the American population, it is not known whether such interethnic differences exist in other populations. To test this possibility, we examined the distribution of genetic variants of three clinically relevant eNOS polymorphisms (T(-786)C in the promoter, the VNTR in intron 4, and the Glu298Asp variant in exon 7) in 136 black and 154 white subjects from a Brazilian population, which is very heterogeneous. We also estimated the haplotype frequency and evaluated associations between these variants. The Asp298 variant was more common in whites (32.8%) than in blacks (15.1%) (P < 0.004). Similarly, the C(-786) variant was more common in whites (41.9%) than in blacks (19.5%) (P < 0.0004). However, the 4a variant was more common in blacks (32.0%) than in whites (17.9%) (P < 0.003). The most common predicted haplotype in both ethnic groups combined only wild-type variants. While the second most common haplotype in blacks includes the variant 4a and the wild-type variants for the remaining polymorphisms, the second most common haplotype in whites includes the variants Asp298 and C(-786) and the wild-type variant for polymorphism in intron 4. The marked interethnic differences that we found in Brazilians are very similar to those previously reported in Americans. These findings strongly suggest a consistent difference in the distribution of eNOS genetic variants in blacks compared with whites and indicate that the interethnic differences do not vary with geographic origin.
authors.affiliation: Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Aline S
authors.initials: AS
authors.lastname: Marroni
authors.forename: Ingrid F
authors.initials: IF
authors.lastname: Metzger
authors.forename: Debora C
authors.initials: DC
authors.lastname: Souza-Costa
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nagassaki
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: Ronan X
authors.initials: RX
authors.lastname: Correa
authors.forename: Fabricio
authors.initials: F
authors.lastname: Rios-Santos
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001483:Base Sequence; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics*
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III