Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men.
OBJECTIVE
Controversy exists regarding the effects of polymorphisms in the endothelial nitric oxide synthase (eNOS) gene on nitrites/nitrates (NOx) plasma concentrations. In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels.


METHODS
We studied 154 healthy subjects (fasting, white males, who were non-smokers, 18-60 years of age, and not taking any medication). Genomic DNA was isolated from blood samples and genotypes were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence.


RESULTS
Haplotype frequencies were compared in two groups of subjects: those with the 30 lowest NOx levels (group L) and those with the 30 highest NOx levels (group H). NOx levels in group L and H were 24.2+/-4.5 microM and 80.9+/-8.9 microM, respectively. Genotype frequencies for the three polymorphisms were not different when the two groups were compared (all P>0.05, chi-squared test). However, the haplotype including the alleles C (promoter), 4b (intron 4), and Glu (exon 7) was significantly more common in group L (16%) than in group H (4%) (P=0.0047). The frequencies of the remaining haplotypes were not different among group L and H.


CONCLUSIONS
While eNOS genotypes are not significantly associated with changes in the circulating NOx concentrations, the specific eNOS haplotype that includes the 'C', '4b', and 'Glu' alleles is associated with lower circulating NOx concentrations.
Metzger
Ingrid F
IF
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Souza-Costa
Debora C
DC
Marroni
Aline S
AS
Nagassaki
Sabrina
S
Desta
Zeruesenay
Z
Flockhart
David A
DA
Tanus-Santos
Jose E
JE
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012016:Reference Values
D017931:DNA Primers; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III