Still Building on Candidate-Gene Strategy in Hypertension?

Abstract

In the general hypertensive population, blood pressure (BP) is a multifactorial trait, and it appears that hypertension results from increments in BP from a number of contributing variants and their interactions with the environment. In spite of numerous linkage and association studies of candidate genes for BP per se, or BP response to salt, the genetic network responsible for BP variation remains elusive. In recent years, several genome-wide scans have been performed in different populations around the world. The results have been rather variable, which can be attributed to different ethnic origins of the populations; often small sample sizes; lack of stratification by gender, age, and other determinants of BP; and limited assessment of the phenotype. However, 6 independent studies have reported evidence of linkage between systolic BP and chromosome 16p12 that includes SCNN1B and SCNN1G .1 In the present issue of Hypertension , Busst et al1 focus attention on the influence of polymorphisms in SCNN1G , the gene encoding the γ-subunit of epithelial sodium channel (ENaC), on systolic BP. Three single nucleotide polymorphisms, considered individually or as a haplotype, appeared to be associated with systolic BP in logistic regression analyses adjusted for age, sex, and body mass index.1 The study was carried out in a white Australian population. This article is particularly attractive, because it confirms the involvement of “natural” susceptibility genes in BP levels. This is a good example of the importance of performing a comprehensive “gene-scan” analysis to determine whether a candidate gene is associated with the phenotype. Haplotype analysis refers to the simultaneous study of multiple alleles, as opposed to the study of single allele at a time. Although it is possible that the causal genetic variant is included in the set of variants/markers tested, the premise for this approach is that ≥1 …