title: Genetic determination of human essential hypertension.
abstract: Recent advances in genetic determination of human essential hypertension (EHT) are discussed by reviewing the candidate genes. Candidate genes have been selected based on genetic information from classical linkage analysis (affected sib-pair analysis) or mendelian hypertension (autosomal dominant inheritance of hypertension). Most of these genes are, directly or indirectly, coupled to salt handling of the kidney, being included in the renin-angiotensin system (RAS), steroid-hormone metabolism, and renal sodium transporters. Angiotensinogen (AGT) gene in RAS was first described as a strong candidate associated with the onset of hypertension, since sib-pair linkage analysis has demonstrated the trait loci for hypertension which includes the coding region for AGT. M235T polymorphism of AGT has been studied extensively in many populations including Japanese, and the results suggest a weak, but significant linkage with hypertension. The presence (insertion [I]) or absence (deletion [D]) of 287bp in intron 16 of angiotensin converting enzyme gene has also been examined in RAS, and the results suggest D polymorphism as a risk factor for hypertension in men. Other components in RAS, such as renin, angiotensinogen II type I receptor, or kallikrein have also been studied, but the available information is still incomplete. Genetic investigations of mendelian hypertension has identified the genetic mechanisms for glucocorticoid remediable aldosteronism, apparent mineral corticoid excess, and Liddle's syndrome as chimeric gene duplications of CYP11B1 (aldosterone synthase gene) and CYP11B2 (11beta-hydroxylase gene), mutations in the gene of 11beta-hydroxysteroid dehydrogenase type 2 that catalyzes the conversion of cortisol to cortisone, and mutations in beta or gamma subunit of epithelial sodium channel (ENaC), respectively. Subsequently, genetic variants of CYP11B2 and beta or gamma subunit of ENaC have been found, suggesting the -344C polymorphism of CYP11B2, 594S variant of betaENaC, and two rare variants of gammaENaC as risk factors for EHT. In spite of the extensive research, haplotypes in individual populations remain to be elucidcated in most candidate genes. Even casual conclusions of possible linkage with EHT need to be further examined with better determinations of phenotypes, such as ambulatory and home blood pressure monitoring or identification of onset of hypertension in cohort studies.
authors: Department of Medicine, Tohoku University School of Medicine, Tohoku University Graduate School of Medicine and Pharmaceutical Science, Sendai, Japan. mmitsu2i@mail.cc.tohoku.ac.jp
authors: M
authors: M
authors: Matsubara
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis; D002352:Carrier Proteins / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006973:Hypertension / Q000235:genetics*; D007610:Kallikreins / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D007705:Kinins / Q000502:physiology; D012084:Renin-Angiotensin System / Q000235:genetics; D012964:Sodium / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007705:Kinins; D000450:Aldosterone; D012964:Sodium; D007610:Kallikreins; D006854:Hydrocortisone