Smoking-dependent and haplotype-specific effects of endothelial nitric oxide synthase gene polymorphisms on angiographically assessed coronary artery disease in Caucasian- and African-Brazilians.
The nitric oxide produced by endothelial nitric oxide synthase (eNOS) plays a pivotal role in protecting the arterial wall from damages and atherosclerosis. The T-786C, the 27-bp repeat in intron 4, and the E298D eNOS gene polymorphisms were studied in 715 Brazilian patients (447 Caucasian- and 268 African-Brazilians) who underwent coronary angiography. The -786C frequency was increased in coronary artery disease (CAD) cases with significant lesions (> or =50% luminal obstruction) when compared with lesion-free controls; this difference was detected in smokers but not in nonsmokers, both in Caucasian- (p=0.011) and African-Brazilians (p=0.005). The interaction between -786C carriers and smoking was an independent CAD predictor (OR: 2.9, 95% CI: 1.4-5.9; p=0.003) in multiple logistic regression. The 298D mutation frequency was also higher among CAD cases (p=0.036) in African-Brazilian smokers, but this effect was not independent from other variables in the regression model. Though not associated with CAD, the 4-repeat allele combined with different T-786C alleles showed protective and susceptible effects in Caucasian-Brazilian smokers. The -786C/4-repeat/298E haplotype frequency was higher (p=0.020), whereas -786T/4-repeat/298E was lower (p=0.023) in these cases. These results showed a smoking-dependent effect of the T-786C eNOS polymorphism on CAD in both Caucasian- and African-Brazilians. Additionally, the haplotype analysis revealed different eNOS haplotypes associated with protection and susceptibility to the disease.
Rios
Domingos L S
DL
Laboratório de Genética Molecular, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Avenida José Moreira Sobrinho, s/n, Bairro-Jequiezinho, 45.200-000 Jequié, BA, Brazil. drios@uesb.br
D'Onofrio
Lorenza O
LO
Souza
Joares K
JK
Queiroz
Amália M
AM
Raduy-Maron
Luciana
L
Silva-Neto
Naila
N
Carvalho
Heitor G
HG
Santos-Filho
Ademar
A
Galvão-Castro
Bernardo
B
D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics; D001938:Brazil; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid; D012907:Smoking / Q000009:adverse effects; D044465:White People / Q000235:genetics
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III