Interaction between -786TC polymorphism in the endothelial nitric oxide synthase gene and smoking for myocardial infarction in Korean population.
BACKGROUND
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilation and antithrombotic action. Controversial results regarding the association of eNOS gene polymorphisms with myocardial infarction (MI) have been reported.


METHODS
A total of 932 individuals living in Seoul and the suburb, Korea, were randomly selected. Genomic DNA was prepared from blood leukocytes. A GT missense mutation in exon 7 (894GT) was screened using PCR-RFLP analysis. The genotypes of 3 mutations (-786TC, -922AG, and -1468TA) in the 5'-flanking region were determined by a minisequencing protocol (SNaPshot), respectively.


RESULTS
Pair-wise linkage analysis revealed that 3 mutations of -786TC, -922AG, and -1468TA were completely linked with each other (mid R:D'mid R:=1, r(2)=0.96-1.0). Furthermore, each of these mutant alleles (-786C, -922G, or -1468A), but not 894T allele, was associated with the risk of MI. Multiple logistic regression analysis revealed that each of these mutant alleles was a predictive independent risk factor for the risk of MI (odds ratio, 1.69 for dominant effects, P<0.05) after age and sex adjustments. Smoking further increased the odds ratio by 2.04 for the risk of MI when it was combined with the mutant alleles.


CONCLUSIONS
Each of 3 mutations (-786TC, -922AG, or -1468TA) in the 5'-flanking region of eNOS gene may play a role in the pathogenesis of MI in Korean population, and also provides an evidence for a significant interaction between these mutations and smoking.
Jo
Inho
I
Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul 122-701, South Korea. inhojo@nih.go.kr
Moon
Jesung
J
Yoon
Suin
S
Kim
Hung-Tae
HT
Kim
Eunkyung
E
Park
Hyun-Young
HY
Shin
Chol
C
Min
Jiho
J
Jin
Yoon-Mi
YM
Cha
Seung-Hun
SH
Jo
Sangmee Ahn
SA
D000368:Aged; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
D017931:DNA Primers; D052250:Nitric Oxide Synthase Type III