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Open Access Original investigation

PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the population based KORA S4-Cohort

Bernd Stratmann1, Tao Xu2, Christa Meisinger3, Barbara Menart4, Michael Roden4, Christian Herder4, Harald Grallert2, Annette Peters3, Wolfgang Koenig5, Thomas Illig26, Heinz-Erich Wichmann78, Rui Wang-Sattler2, Wolfgang Rathmann9 and Diethelm Tschoepe1*

Author Affiliations

1 Heart and Diabetes Center NRW, Ruhr University Bochum, Georgstr. 11, D-32545 Bad Oeynhausen, Germany

2 Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center of Environmental Health, Neuherberg, Germany

3 Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center of Environmental Health, Neuherberg, Germany

4 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Duesseldorf, Germany

5 Department Internal Medicine II, University Clinic Ulm, Ulm, Germany

6 Hannover Unified Biobank, Hannover Medical School, Hannover, Germany

7 Institute of Epidemiology I, Helmholtz Zentrum Muenchen, German Research Center of Environmental Health, Neuherberg, Germany

8 Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany

9 Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Duesseldorf, Germany

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Cardiovascular Diabetology 2014, 13:90  doi:10.1186/1475-2840-13-90

Published: 5 May 2014

Abstract

Objective

The genetic polymorphism concerning the ß3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.

Research design and methods

Population-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.

Results

Prevalence of thrombogenic allele variant PLA2 was 15.0%. Multivariate analysis revealed no association between PLA1A2 polymorphism and mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55–75 years). PLA1A2 was significantly associated with elevated HbA1c levels in diabetic patients (N = 209) and reduced mean platelet volume in general population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA1c.

Conclusion

PLA1A2 polymorphism is associated with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5% (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are therefore regarded as effective primary prevention in this group.

Keywords:
Glycated hemoglobin; Platelet glycoprotein receptor polymorphism; Mean platelet volume; All-cause mortality; Glycemic management; Epidemiology