Linkage analysis of endothelial nitric oxide synthase gene with human blood pressure

Objective Endothelial nitric oxide exerts important effects on the regulati on of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hyperte nsion. To examine whether the region encoding the eNOS gene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population. Design In healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotyp es, with both parametric and non-parametric and single-locus and multi-poin t methods. Methods We selected 260 families comprising mother and father (aged 40-70 y ears) and two natural offspring (aged 18-30 years) from the Victorian Famil y Heart Study. After standardized measurement of clinical data and extracti on of DNA, all family members were genotyped at five microsatellite loci in cluding the CA repeat in the eNOS gene by a PCR method. The quantitative li nkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS. Results With both linkage analyses, we found no linkage between any of the loci on chromosom e 7q35-36 and the phenotypes systolic and diastolic blood pressure, mean ar terial pressure, pulse pressure, pulse rate, weight, height and body mass i ndex. Conclusion Based on these results, we conclude that in this population the eNOS gene is not linked to the physiological variation of blood pressure an d other related phenotypes. J Hypertens 1999, 17:1431-1436 (C) Lippincott W illiams & Wilkins.