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Multivariate meta-analysis of the association of G-protein beta 3 gene (GNB3) haplotypes with cardiovascular phenotypes |
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| Authors: | Tiago V Pereira Lilian Kimura Yasushi Suwazono Hideaki Nakagawa Makoto Daimon Toshihide Oizumi Takamasa Kayama Takeo Kato Liao Li Shufeng Chen Dongfeng Gu Wilfried Renner Winfried März Yoshiji Yamada Pantelis G Bagos Regina C Mingroni-Netto |
| Institution: | 1. Health Technology Assessment Unit, Institute of Education and Health Sciences, German Hospital Oswaldo Cruz, S?o Paulo, Brazil 2. Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de S?o Paulo, CP 11461, S?o Paulo, SP, 05422-970, Brazil 3. Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan 4. Department of Epidemiology and Public Health, Kanazawa Medical University, Uchinada, Ishikawa, Japan 5. Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology (DNHMED), Yamagata University School of Medicine, Yamagata, Japan 6. Global Center of Excellence Program Study Group, Yamagata University School of Medicine, Yamagata, Japan 7. Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori, Japan 8. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China 9. Prevention, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 10. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria 11. Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany 12. Synlab Academy, Synlab Services GmbH, Mannheim, Germany 13. Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan 14. Department of Computer Science and Biomedical Informatics, University of Central Greece, Lamia, Greece |
| Abstract: | The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation–maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy–Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects “pooled” analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI. |
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