Molecular Biology Reports

, Volume 41, Issue 5, pp 3113–3125 | Cite as

Multivariate meta-analysis of the association of G-protein beta 3 gene (GNB3) haplotypes with cardiovascular phenotypes

  • 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


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.


Meta-analysis Haplotypes GNB3 Polymorphism Hypertension 



This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil, to T.V.P.). This work was also supported in part by the Global Center of Excellence Program (No. F03, to M.D.) founded by the Japan Society for the Promotion of Science, Japan (to Y.S.) and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Numbers 18209023, 18018021, and 19659149 to Y.Y.).

Conflict of interest


Supplementary material

11033_2014_3171_MOESM1_ESM.doc (428 kb)
Supplementary material 1 (DOC 428 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Tiago V. Pereira
    • 1
    • 2
  • Lilian Kimura
    • 2
  • Yasushi Suwazono
    • 3
  • Hideaki Nakagawa
    • 4
  • Makoto Daimon
    • 5
    • 6
    • 7
  • Toshihide Oizumi
    • 5
  • Takamasa Kayama
    • 6
  • Takeo Kato
    • 5
    • 6
  • Liao Li
    • 8
  • Shufeng Chen
    • 9
  • Dongfeng Gu
    • 9
  • Wilfried Renner
    • 10
  • Winfried März
    • 10
    • 11
    • 12
  • Yoshiji Yamada
    • 13
  • Pantelis G. Bagos
    • 14
  • Regina C. Mingroni-Netto
    • 2
  1. 1.Health Technology Assessment Unit, Institute of Education and Health SciencesGerman Hospital Oswaldo CruzSão PauloBrazil
  2. 2.Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de BiociênciasUniversidade de São PauloSão PauloBrazil
  3. 3.Department of Occupational and Environmental Medicine, Graduate School of MedicineChiba UniversityChibaJapan
  4. 4.Department of Epidemiology and Public HealthKanazawa Medical UniversityUchinadaJapan
  5. 5.Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology (DNHMED)Yamagata University School of MedicineYamagataJapan
  6. 6.Global Center of Excellence Program Study GroupYamagata University School of MedicineYamagataJapan
  7. 7.Department of Endocrinology and MetabolismHirosaki University Graduate School of MedicineAomoriJapan
  8. 8.Institute of BiophysicsChinese Academy of SciencesBeijingChina
  9. 9.Prevention, Cardiovascular Institute and Fu Wai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  10. 10.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University GrazGrazAustria
  11. 11.Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty MannheimUniversity of HeidelbergHeidelbergGermany
  12. 12.Synlab AcademySynlab Services GmbHMannheimGermany
  13. 13.Department of Human Functional Genomics, Life Science Research CenterMie UniversityTsuJapan
  14. 14.Department of Computer Science and Biomedical InformaticsUniversity of Central GreeceLamiaGreece

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