Linkage Analysis of Candidate Genes and Gene-Gene Interactions in Chinese Hypertensive Sib Pairs

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 33; no. 6; pp. 1332 - 1337
• Main Authors: Niu, Tianhua, Xu, Xiping, Cordell, Heather J, Rogus, John, Zhou, Yusheng, Fang, Zhian, Lindpaintner, Klaus
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.1999; Hagerstown, MD Lippincott
• Subjects: Angiotensinogen - genetics; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Calmodulin-Binding Proteins - genetics; Cardiology. Vascular system; China; Chromosome Mapping; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cohort Studies; Epithelial Sodium Channels; Ethnic Groups - genetics; Genetic Markers; Humans; Hypertension - genetics; Kallikreins - genetics; Medical sciences; Microsatellite Repeats; Models, Genetic; Nuclear Family; Pedigree; Renin - genetics; Sodium Channels - genetics; China; Human; Hypertension; Linkage; Gene; Gene interaction; Cardiovascular disease; Chinese; Sibling; Genetic determinism
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.33.6.1332

Previous studies of hypertension in humans and experimental animal models have identified a number of candidate genes that have since been implicated as possibly contributing to essential hypertension. Among them are the genes encoding angiotensinogen, renin, the beta- and gamma-subunits of the epithelial sodium channel (beta/gamma-ENaC), alpha-adducin, and kallikrein (KLK). To examine the role of possible contribution of these genes in ethnic Chinese, as well as the epistatic interaction among them, we studied a large cohort of hypertensive sib pairs from China. DNA samples from 310 concordant affected sibling pairs with hypertension were tested for linkage with the use of excess allele-sharing algorithms based on genotyping with highly informative GT-repeat microsatellite markers localized in the immediate vicinity of the genes encoding angiotensinogen, renin, beta- and gamma-ENaC, alpha-adducin, and KLK. Affected sib pair analysis conducted according to 3 different methods (Statistical Analysis for Genetic Epidemiology [S.A.G.E.]/SIBPAL, MAPMAKER/SIBS, and affected pedigree member [APM] methods) revealed no evidence for linkage of any of these genes to primary hypertension in the population studied. Moreover, 2-locus sib pair linkage analyses to test for gene-gene interactions among each possible pair of candidate genes failed to yield any statistically significant results. Our findings provide no support for a significant contribution of the angiotensinogen, renin, beta/gamma-ENaC, alpha-adducin, or KLK genes, alone or in concert, to the pathogenesis of essential hypertension among Chinese. Our results emphasize the possible role of ethnic differences for complex disease genetics, as well as the need for large, well-characterized investigations. (Hypertension. 1999;33:1332-1337.)