Genetic analysis in human hypertension.
Hypertension is considered to be a complex trait to which genetic, environmental, and demographic factors contribute interactively. Recently, molecular genetic studies have achieved remarkable success in the elucidation of causative mutations in several Mendelian hypertensive disorders in which single nucleotide polymorphisms (SNPs) disrupt the function of single genes, thereby leading to unambiguous phenotypes. It seems unlikely, however, that such a simple base-substitution is the primary mechanism in cases of essential hypertension, even if SNPs modify the relevant gene function to some extent. Despite the enormous efforts made to date, no consistent association between any of the candidate genes and essential hypertension has been established. One plausible explanation is that because individual genes play a modest role in the pathogenesis of hypertension, confounding variables, whether individual (sex, ethnic origin, etc.) or environmental, may decrease the chance of identifying a causative relation between the genes and hypertension, depending on the populations studied. Several approaches can be proposed to overcome this problem, including long-term follow-up of clinical events collected to attain sufficient phenotypic information and statistical power. With the recent advances in high-throughput genotyping techniques and bioinformatic strategies, it has become possible to perform even SNP-based genome-wide screening. At present, however, the need for identification of susceptibility genes for hypertension still poses a great and unanswered challenge. Nonetheless, we believe that a precise understanding of the manner in which genetic variations affect hypertension can be achieved, and that clarification of the associated phenotypes will lead to the development of effective preventive and treatment strategies.
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, Tokyo. nokato@ri.imcj.go.jp
Norihiro
N
Kato
D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D008040:Genetic Linkage; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D051381:Rats; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics
D022702:Receptors, Adrenergic, beta-3; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A