This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Niu, T. Articles by Lindpaintner, K. Search for Related Content PubMed PubMed Citation Articles by Niu, T. Articles by Lindpaintner, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Clinical genetics Other hypertension Ion channels/membrane transport

(Hypertension. 1999;33:1332-1337.)
© 1999 American Heart Association, Inc.

Scientific Contributions

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

Tianhua Niu; Xiping Xu; Heather J. Cordell; John Rogus; Yusheng Zhou; Zhian Fang; Klaus Lindpaintner

From the Cardiovascular Division (T.N., K.L.) and the Channing Laboratory (X.X., J.R.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; Department of Cardiology, The Children's Hospital, Harvard Medical School (T.N., K.L.); Program for Population Genetics (T.N., X.X., J.R.) and Division of Biological Sciences (T.N., X.X., J.R., K.L.), Harvard School of Public Health, Boston, Mass; Anhui Research Institute for Biomedical Sciences and Environmental Health, Anhui, China (X.X., Y.Z., Z.F.); Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio (H.J.C.); and Max Delbrück Center for Molecular Medicine, Berlin, Germany (K.L.).

Abstract—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 ß- and -subunits of the epithelial sodium channel (ß/-ENaC), -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, ß- and -ENaC, -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, ß/-ENaC, -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.

Key Words: renin • sodium channels • adducin • kallikrein • hypertension, essential • genetics • Chinese

This article has been cited by other articles:

				M. H. Zafarmand, Y. T. van der Schouw, D. E. Grobbee, P. W. de Leeuw, and M. L. Bots {alpha}-Adducin Gly460Trp Variant Increases the Risk of Stroke in Hypertensive Dutch Women Hypertension, June 1, 2008; 51(6): 1665 - 1670. [Abstract] [Full Text] [PDF]

				P. Manunta and G. Bianchi Pharmacogenomics and Pharmacogenetics of Hypertension: Update and Perspectives--The Adducin Paradigm J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S30 - S35. [Abstract] [Full Text] [PDF]

				G. Bianchi Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1536 - R1549. [Abstract] [Full Text] [PDF]

				G. Bianchi, P. Ferrari, and J. A. Staessen Adducin Polymorphism: Detection and Impact on Hypertension and Related Disorders Hypertension, March 1, 2005; 45(3): 331 - 340. [Abstract] [Full Text] [PDF]

				T. A. Kotchen, U. Broeckel, C. E. Grim, P. Hamet, H. Jacob, M. L. Kaldunski, J. M. Kotchen, N. J. Schork, P. J. Tonellato, and A. W. Cowley Jr Identification of Hypertension-Related QTLs in African American Sib Pairs Hypertension, November 1, 2002; 40(5): 634 - 639. [Abstract] [Full Text] [PDF]

				Y. R. Su and A. G. Menon Epithelial Sodium Channels and Hypertension Drug Metab. Dispos., April 1, 2001; 29(4): 553 - 556. [Abstract] [Full Text]

				H. Schmidt, F. Fazekas, G. M. Kostner, C. M. van Duijn, and R. Schmidt Angiotensinogen Gene Promoter Haplotype and Microangiopathy-Related Cerebral Damage : Results of the Austrian Stroke Prevention Study Stroke, February 1, 2001; 32(2): 405 - 412. [Abstract] [Full Text] [PDF]

				M. L. Marro, O. U. Scremin, M. C. Jordan, L. Huynh, F. Porro, K. P. Roos, S. Gajovic, F. E. Baralle, and A. F. Muro Hypertension in {beta}-Adducin-Deficient Mice Hypertension, September 1, 2000; 36(3): 449 - 453. [Abstract] [Full Text] [PDF]

				S. M. Williams, J. H. Addy, J. A. Phillips III, M. Dai, J. Kpodonu, J. Afful, H. Jackson, K. Joseph, F. Eason, M. M. Murray, et al. Combinations of Variations in Multiple Genes Are Associated With Hypertension Hypertension, July 1, 2000; 36(1): 2 - 6. [Abstract] [Full Text] [PDF]