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Worldwide Ethnic Distribution of the G Protein ß3 Subunit 825T Allele and Its Association with Obesity in Caucasian, Chinese, and Black African Individuals

WINFRIED SIFFERT^*, PETER FORSTER^**, KARL-HEINZ JÖCKEL, DAVID A. MVERE, BERND BRINKMANN^**, CHRISTOPH NABER^*, ROBERT CROOKES, ANTHON DU P. HEYNS, JÖRG T. EPPLEN^§§, JOY FRIDEY^||||, BARRY I. FREEDMAN^¶¶, NORBERT MÜLLER, DIETMAR STOLKE^¶, ARYA M. SHARMA^##, KHALAF AL MOUTAERY^***, HANS GROSSE-WILDE^§, BETTINA BUERBAUM^*, TANJA EHRLICH^*, HAKIMUDDIN RAZI AHMAD, BERNHARD HORSTHEMKE^||, ERNETTE D. DU TOIT, ANJA TIILIKAINEN^§§§, JUNBO GE^#, YULIN WANG^||||||, DONGLIANG YANG^¶¶¶, JOHANNES HÜSING and DIETER ROSSKOPF^*

^* Institute für Pharmakologie, Universitätsklinikum Essen, Essen, Germany
Institute für Medizinische Informatik, Biometrie und Epidemiologie, Universitätsklinikum Essen, Essen, Germany
Institute für Transfusionsmedizin
^§ Institute für Immunologie, Universitätsklinikum Essen, Essen, Germany
^|| Institute für Humangenetik, Universitätsklinikum Essen, Essen, Germany
^¶ Institute für Klinik für Neurochirurgie Universitätsklinikum Essen, Essen, Germany
^# Institute für Abteilung für Kardiologie, Universitätsklinikum Essen, Essen, Germany
^** Institut für Rechtsmedizin, Universität Münster, Münster, Germany
National Blood Transfusion Service Zimbabwe, Avondale, Harare, Zimbabwe
The South African Blood Transfusion Service, Johannesburg, South Africa
^§§ Molekulare Humangenetik, Ruhr-Universität, Bochum, Germany
^|||| Blood Bank of San Bernardino and Riverside Counties, San Bernardino, California
^¶¶ Section on Nephrology, Department of Medicine, Bowman Gray School of Medicine, Winston-Salem, North Carolina
^## Universitätsklinikum Benjamin Franklin, Abteilung für Endokrinologie und Nephrologie, Berlin, Germany
^*** Riyadh Armed Forces Hospital, Division of Neurosurgery, Riyadh, Saudi Arabia
The Aga Khan University, Department of Physiology and Pharmacology, Karachi, Pakistan
Laboratory for Tissue Immunology, Falmouth Building, Medical School, Cape Town, South Africa
^§§ Departement of Clinical Microbiology and Immunology, University of Oulu, Oulu, Finland
^|||| Department of Pediatrics, Shandong Provincial Hospital, Jinan, Shandong, People's Republic of China
^¶¶ Division of Clinical Immunology, Tongji Medical University, Wuhan, People's Republic of China.

Correspondence to Dr. Winfried Siffert, Institut für Pharmakologie, Universitätsklinikum, Hufelandstrasse 55, D-45122 Essen, Germany. Phone: +49 201 723 3470; Fax: +49 201 723 5968; E-mail: winfried.siffert{at}uni-essen.de

Abstract

Abstract. Recently, it was demonstrated that one allele (825T) of the gene encoding the G protein ß3 subunit (GNB3) is associated with hypertension in Germans. This study investigates a possible association with obesity in young male Germans, Chinese, and black South Africans with low, intermediate, and high 825T allele frequencies, respectively. In each of these three distinct cohorts, the 825T allele frequency was increased significantly in overweight (body mass index [BMI] 25 kg/m²) and obese individuals (BMI >27 kg/m²) compared to those with normal weight. The 825T allele frequencies in these three BMI groups were, respectively, 29.5, 39.3, and 47.7% in Germans, 46.8, 53.9, and 58.6% in Chinese, and 83.1, 87.7, and 90.9% in South Africans. In each of these three distinct groups, the 825T allele was significantly associated with obesity with odds ratios between 2 and 3. More urban than rural black Africans were overweight despite similar 825T allele frequencies in both populations, which underscores the role of both genetic and environmental factors. BP values in young male whites increased significantly with increasing BMI values but were independent of the C825T polymorphism, suggesting that hypertension associated with the 825T allele could be a consequence of obesity. Genotyping of 5254 individuals from 55 native population samples from Africa, the Americas, Europe, Asia, Australia, and New Guinea demonstrated highest 825T allele frequencies in black Africans (82%) and intermediate values in east Asians (47%). It is anticipated that high frequencies of the 825T allele in Africans and Asians may contribute to an obesity and hypertension epidemic if Westernization of lifestyles continues.

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