The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health Study

März, Winfried; Boehm, Bernhard O.; Winkelmann, Bernhard R.; Hoffmann, Michael M.

doi:10.1007/s00125-004-1557-6

Cited by 6 publications

(8 citation statements)

References 16 publications

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“…This finding is in contrast to a later publication of Maerz and coworkers from the Ludwigshafen Risk and Cardiovascular Health Study which revealed no association of the GPIIIa PLA1A2 polymorphism with type 2 diabetes, glucose metabolism, angiographically proven CHD or myocardial infarction [24]. …”

Section: Introductioncontrasting

confidence: 95%

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

Stratmann

Meisinger

et al. 2014

Cardiovasc Diabetol

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ObjectiveThe 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 methodsPopulation-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.ResultsPrevalence 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.ConclusionPLA1A2 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.

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Section: Introductioncontrasting

confidence: 95%

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

Stratmann

Meisinger

et al. 2014

Cardiovasc Diabetol

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“…Analysis of the association between carriage of the PlA2 allele and MI using data adjusted for age, sex, ethnicity and cardiovascular risk factors demonstrated an increased level of association ( n = 12,001; OR 1.240, 95% CI 1.117–1.376; p<0.001) [87], [88], [96], [97], [101], [109], [110], [112], [119]–[121], [125], [127]. Further subgroup analysis based on comparison of the PlA1/A1 versus PlA2/A2 genotype failed to show a significant association ( n = 23,836; OR 1.023, 95% CI 0.877–1.192; p = 0.774) [70]–[72], [81], [82], [86]–[91], [95], [98]–[100], [102]–[104], [106]–[108], [111]–[114], [116], [117], [120], [122], [124], [128] (Figure 3); however, within this analysis, the number of subjects with the PlA2/A2 genotype was small, consisting of 333 cases and 1,504 controls.…”

Section: Resultsmentioning

confidence: 99%

“…Analysis based on ethnicity was limited to Caucasians as the majority of studies did not explicitly state the ethnicity of participants. A non-significant pooled OR for the association of PlA2 carriage with MI was observed for the 11 available studies ( n = 10,585; OR 1.050, 95% CI 0.962–1.146; p = 0.272) [71], [81], [88], [95]–[97], [103], [109], [112], [127], [128].…”

Section: Resultsmentioning

confidence: 99%

“…Cohort studies did not demonstrate an association between carriage of the PlA2 allele and MI ( n = 19,032; OR 0.996, 95% CI 0.917–1.082; p = 0.926) [80], [85], [86], [92]–[95], [97], [100], [105], [106], [109], [112], [114], [118], [125], [126], whereas case-control studies did ( n = 21,660; OR 1.126, 95% CI 1.057–1.198; p<0.001) (Figure 6) [70]–[73], [81]–[84], [87]–[91], [96], [98], [99], [101]–[104], [107], [108], [110], [111], [113], [115]–[117], [119]–[124], [127], [128]. Studies with <250 cases showed a significant association ( n = 10,145; OR 1.240, 95% CI 1.139–1.350; p = 0.006) [70], [72], [73], [80]–[83], [85], [88]–[94], [97], [98], [102], [103], [105], [108], [110], [111], [113]–[116], [118]–[127], [130], whereas studies with ≥250 cases did not ( n = 30,547; OR 0.999, 95% CI 0.935–1.084; p = 0.864) …”

Section: Resultsmentioning

confidence: 99%

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The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

2014

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BackgroundThe PlA2 polymorphism of glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI.MethodsElectronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally.Findings57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05).ConclusionsThe presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and MI is true for the total population studied. However for younger subjects, the relative absence of conventional cardiovascular risk factors results in a significant association between carriage of the PlA2 allele and MI.

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“…27 Studies on the association of the PlA1/ A2 polymorphism of glycoprotein IIIa and type 2 diabetes have reported conflicting results 17,28,29 (Table 54.6). It has been suggested that the function of platelet GPIIIa is modulated by a cysteine protease, calpain 10, which is not characteristic of platelets.…”

Section: Genetic Factors and Glycoprotein Iib-iiiamentioning

confidence: 99%

Effects of Environmental, Genetic, and Epigenetic Factors on Platelet Glycoproteins and the Development of Diabetic Retinopathy

Petrovič

2014

Handbook of Nutrition, Diet and the Eye

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The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health Study

Cited by 6 publications

References 16 publications

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

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

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

Effects of Environmental, Genetic, and Epigenetic Factors on Platelet Glycoproteins and the Development of Diabetic Retinopathy

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