title: PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the population based KORA S4-Cohort.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stratmann
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Menart
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: Heart and Diabetes Center NRW, Ruhr University Bochum, Georgstr, 11, D-32545 Bad Oeynhausen, Germany. diethelm.tschoepe@ruhr-uni-bochum.de.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D054466:Phospholipases A1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods; D011236:Prediabetic State / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D006442:Glycated Hemoglobin; D054466:Phospholipases A1; C517652:hemoglobin A1c protein, human; C512665:PLA1A protein, human