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An affected pedigree member analysis of linkage between the dopamine D2 receptor gene TaqI polymorphism and obesity and hypertension.

Fang YJ, Thomas GN, Xu ZL, Fang JQ, Critchley JA, Tomlinson B

Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.

BACKGROUND: Dopamine modulates a variety of physiological functions including natriuresis and satiety. We have previously reported that the TaqI polymorphism of the dopamine D2 receptor (DD2R) gene is associated with both blood pressure and obesity indices in a normoglycaemic Hong Kong Chinese population. In this study, we present evidence confirming the linkage between this gene polymorphism, obesity and hypertension. METHODS: Two hundred and seventy-four siblings from 96 normoglycaemic hypertensive families were recruited, including 133 who were hypertensive. Central obesity was defined as a waist-to-hip ratio of > or = 0.9 and > or = 0.85 in males and females, respectively, and was identified in 99 of the siblings. The DD2R gene TaqI polymorphism was identified with a polymerase chain reaction based restriction fragment length polymorphism protocol. The affected pedigree member (APM) linkage analysis (sib-pair program, version 0.99.9, by D.L. Duffy) was used to assess for linkage between this gene polymorphism, obesity and hypertension in 73 families with siblings discordant for hypertension. RESULTS: The A1 allele frequencies were similar in the 133 hypertensive, and 141 normotensive siblings, including the 99 centrally obese siblings at 0.431, 0.421 and 0.418, respectively. APM linkage analysis suggested that the DD2R gene TaqI polymorphism had evidence of linkage with blood pressure (T = -1.86, P = 0.013), as well as with obesity (T = -1.58, P = 0.007). CONCLUSION: Our data in normoglycaemic Hong Kong Chinese supports that the DD2R gene TaqI polymorphism is a marker associated with the pathogenesis of obesity and hypertension.

Published 7 June 2005 in Int J Cardiol, 102(1): 111-6.
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