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Thromb Haemost 2009; 101(02): 351-358
DOI: 10.1160/TH08-05-0284
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Association between polymorphisms in the β2-adrenergic receptor gene with myocardial infarction and ischaemic stroke in women

Markus Schürks
1   Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
6   Department of Neurology, University Hospital Essen, Essen, Germany
,
Tobias Kurth
1   Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
2   Division of Aging, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
3   Department of Epidemiology, Harvard School of Public Health, Boston, Massachussetts, USA
5   INSERM Unit 708, Neuroepidemiology and University Pierre et Marie Curie, Paris, France
,
Paul M. Ridker
1   Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
3   Department of Epidemiology, Harvard School of Public Health, Boston, Massachussetts, USA
,
Julie E. Buring
1   Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
2   Division of Aging, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
3   Department of Epidemiology, Harvard School of Public Health, Boston, Massachussetts, USA
4   Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachussetts, USA
,
Robert Y. L. Zee
1   Division of Preventive Medicine, Department of Medicine; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA
› Author AffiliationsFinancial support: The Women’s Health Study is supported by grants from the National Heart, Lung, and Blood Institute (HL-43851; HL-080467), and the National Cancer Institute (CA-47988). The research for this work was supported by grants from the Donald W. Reynolds Foundation, the Leducq Foundation, and the Doris Duke Charitable Foundation. The authors also thank F. Hoffmann La-Roche and Roche Molecular Systems, Inc. for supporting the genotype-determination financially and with in-kind contribution of reagents and consumables. Dr. Schürks was supported by a grant from the Deutsche Forschungsgemeinschaft. The funding agencies played no role in the design, conduct, data management, analysis, or manuscript preparation related to this manuscript.
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Publication History

Received: 05 May 2008

Accepted after major revision: 05 January 2008

Publication Date:
23 November 2017 (online)

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Summary

Results from studies investigating the association between polymorphisms in the β2-adrenergic receptor gene (ADRB2) and cardiovascular disease (CVD) are controversial. Using haplo-type-based analysis, we have previously shown a protective effect of the Gly16-Gln27-Ile164 haplotype on myocardial infarction in men. We sought to replicate these findings in women and further investigated whether the gene variants exert differential effects on myocardial infarction and ischaemic stroke. We performed a prospective study among 25,224 women, participating in the Women’s Health Study and free of CVD at study entry. We had information on polymorphisms Gly16Arg, Gln27Glu, and Thr164Ile in the ADRB2. Incident CVD was self-reported and confirmed after medical record review. We used proportional hazards models to investigate the association between genotypes and haplotypes with any myocardial infarction, any ischaemic stroke, and CVD death. During a mean of 11.8 years of follow-up, 274 myocardial infarctions, 299 ischaemic strokes, and 159 CVD deaths occurred. Among the whole cohort genotypeand haplotype-based analyses did not show an association for any of the gene variants with any of the CVD outcomes. When we focused on Caucasian women, the haplotype-based analysis, however, suggested an inverse association of the haplotype Gly16-Gln27-Thr164 with incident myocardial infarction (multivariable-adjusted hazard ratio 0.75; 95% confidence interval 0.58–0.97; p=0.03). We did not find associations in the haplo-type-based analyses with incident ischaemic stroke or CVD death. Our results suggest that the haplotype Gly16-Gln27-Thr164 is associated with reduced risk of incident myocardial infarction but not ischaemic stroke in Caucasian women and suggest differential pathophysiologies for myocardial infarction and stroke.

Keywords

β2-adrenergic receptor gene - ischaemic stroke - myocardial infarction - polymorphism