The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene

Abstract

Glycoprotein IIIa (GpIIIa) is a membrane receptor, found in various tissues, that has two alleles: A1 and A2. Signalling cascade of GpIIIa is modulated by enzymes called calpains, proteases that may also influence glucose metabolism. There is one small study that shows a high association of A1/A2 polymorphism with type 2 diabetes mellitus. In our research we planned to evaluate the association of A1/A2 polymorphism with type 2 diabetes in a population of patients with ST elevation acute myocardial infarction (STEMI). The study comprised 352 individuals. From the cohort of patients hospitalised for STEMI we chose 113 patients with diagnosed diabetes (diabetic group) and 118 patients with STEMI and normal glucose metabolism (non-diabetic group). The population group consisted of 121 persons. Genotyping was performed by the restriction fragments length polymorphism (RFLP) method. The frequency of alleles in all groups was in Hardy-Weinberg equilibrium. The percentage of A2 allele carriers was comparable among all groups : 20.4% (diabetic patients), 23.7% (nondiabetic) and 21.5% (control group) (p>0.05). There was no significant difference in frequency of A2 allele among the groups. We have not observed any association between GpIIIa polymorphism with either type 2 diabetes or STEMI.

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

“…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].…”

“…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) …”

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

“…Following the activation of platelets by agonists such as ADP, thrombin, or collagen, inside-out 3 signaling occurs, giving rise to the exposure of the ligand binding site of GPIIb-IIIa. 17 The mentioned polymorphism can influence both platelet activation and aggregation 21 and affect postoccupancy signaling by the platelet fibrinogen receptor IIb/IIIa. 19,20 Both GPIIb and GPIIIa are known to bear a number of single amino acid substitutions affecting conformational changes and the ligand binding function with little or no effect on platelet function.…”

“…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.…”

A1/A2 polymorphism of the glycoprotein IIIa gene and diabetic retinopathy in Caucasians with type 2 diabetes

“…A platelet‐specific antigen (PlA1/A2) polymorphism has been by far the most investigated GPIIIa gene polymorphism. A substitution of cytosine for thymidine at position 1565 in exon 2 of GPIIIa gene leads to an amino acid difference at position 33: a leucine (A1 allele) or a proline (A2 allele) 1 . The mentioned polymorphism can influence both platelet activation and aggregation 10–12 and affect post occupancy signalling by the platelet fibrinogen receptor IIb/IIIa 13 .…”