Association analysis of endothelial nitric oxide synthase gene polymorphism with primary hypertension in a Singapore population

• Published in: Journal of human hypertension Vol. 20; no. 12; pp. 956 - 963
• Main Authors: MOE, K. T, LIM, S. T, WONG, P, CHUA, T, DESILVA, D. A, KOH, T. H, WONG, M. C, CHIN-DUSTING, J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01-12-2006; Nature Publishing Group
• Subjects: Alleles; Arterial hypertension. Arterial hypotension; Association analysis; Biological and medical sciences; Blood and lymphatic vessels; Blood flow; Blood Pressure; Body Mass Index; Cardiology. Vascular system; Cardiovascular disease; Care and treatment; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Coronary artery; Diabetes Mellitus - genetics; Diagnosis; Dyslipidemias - genetics; Endothelial cells; Essential hypertension; Experimental diseases; Female; Gene amplification; Gene polymorphism; Genetic polymorphisms; Genotype; Genotype & phenotype; Health aspects; Heart diseases; Humans; Hypertension; Hypertension - genetics; Male; Medical sciences; Middle Aged; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; Polymorphism; Polymorphism, Genetic; Regression analysis; Restriction fragment length polymorphism; Risk factors; Singapore; Susceptibility; Singapore; Hypertension; Singapore; Intron; intron 4 VNTR; Enzyme; primary hypertension; Cardiovascular disease; endothelial nitric oxide synthase; Oxidoreductases; Nitric-oxide synthase; Polymorphism
• ISSN: 0950-9240; 1476-5527
• DOI: 10.1038/sj.jhh.1002096

Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P = 0.035), but disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419 and P = 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P = 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.