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

Objective: The genetic polymorphism concerning the beta 3-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 HbA(1c), 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. HbA(1c) was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA(1c) = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55-75 years). PLA1A2 was significantly associated with elevated HbA(1c) 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 HbA(1c) > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA(1c). Conclusion: PLA1A2 polymorphism is associated with mortality in participants with HbA(1c) 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.