Published Online
on January 22, 2007

A more recent version of this article appeared on March 1, 2007

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Submitted on July 17, 2006
Revised on August 14, 2006

High-Resolution Mapping for Essential Hypertension Using Microsatellite Markers

Keisuke Yatsu; Nobuhisa Mizuki; Nobuhito Hirawa; Akira Oka; Norihiko Itoh; Takahiro Yamane; Momoko Ogawa; Tadashi Shiwa; Yasuharu Tabara; Shigeaki Ohno; Masayoshi Soma; Akira Hata; Kazuwa Nakao; Hirotsugu Ueshima; Toshio Ogihara; Hitonobu Tomoike; Tetsuro Miki; Akinori Kimura; Shuhei Mano; Jerzy K. Kulski; Satoshi Umemura^*; and Hidetoshi Inoko

From the Departments of Medical Science and Cardiorenal Medicine (K.Y., N.H., M.O., T.S., S.U.) and Ophthalmology (N.M., N.I., T.Y., S.O.), Yokohama City University School of Medicine, Yokohama, Japan; Department of Molecular Life Science (K.Y., A.O., J.K.K., H.I.), Course of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Japan; Department of Geriatric Medicine (Y.T., T.M.), School of Medicine, Ehime University, Ehime, Japan; Second Department of Internal Medicine (M.S.), Nihon University School of Medicine, Tokyo, Japan; Department of Public Health (A.H.), Chiba University Graduate School of Medicine, Chiba, Japan; Department of Medicine and Clinical Science (K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Health Science (H.U.), Shiga University of Medical Science, Shiga, Japan; Department of Geriatric Medicine (T.O.), Osaka University Graduate School of Medicine, Osaka, Japan; National Cardiovascular Center (H.T.), Osaka, Japan; Department of Molecular Pathogenesis (A.K.), Division of Pathophysiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Institute of National Sciences (S.M.), Nagoya City University, Nagoya, Japan; and the Centre for Bioinformatics and Biological Computing (J.K.K.), School of Information Technology, Murdoch University, Murdoch, Western Australia, Austaralia.

^* To whom correspondence should be addressed. E-mail: umemuras{at}med.yokohama-cu.ac.jp.

Abstract--During the past decade, considerable efforts and resources have been devoted to elucidating the multiple genetic and environmental determinants responsible for hypertension and its associated cardiovascular diseases. The success of positional cloning, fine mapping, and linkage analysis based on whole-genome screening, however, has been limited in identifying multiple genetic determinants affecting diseases, suggesting that new research strategies for genome-wide typing may be helpful. Disease association (case-control) studies using microsatellite markers, distributed every 150 kb across the human genome, may have some advantages over linkage, candidate, and single nucleotide polymorphism typing methods in terms of statistical power and linkage disequilibrium for finding genomic regions harboring candidate disease genes, although it is not proven. We have carried out genome-wide mapping using 18 977 microsatellite markers in a Japanese population composed of 385 hypertensive patients and 385 normotensive control subjects. Pooled sample analysis was conducted in a 3-stage genomic screen of 3 independent case-control populations, and 54 markers were extracted from the original 18 977 microsatellite markers. As a final step, each single positive marker was confirmed by individual typing, and only 19 markers passed this test. We identified 19 allelic loci that were significantly different between the cases of essential hypertension and the controls.

Key words: essential hypertension • genome-wide • association study • Japanese • new candidate regions

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				P.-a. B. Shih and D. T. O'Connor Hereditary Determinants of Human Hypertension: Strategies in the Setting of Genetic Complexity Hypertension, June 1, 2008; 51(6): 1456 - 1464. [Full Text] [PDF]