Role of tissue plasminogen activator and plasminogen activator inhibitor polymorphism in myocardial infarction
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A case–control association study on 229 Myocardial Infarction (MI) patients and 217 healthy controls was carried out to determine the role of tissue-plasminogen activator (t-PA) (Alu-repeat insertion (I)/deletion (D)) and plasminogen activator inhibitor (PAI-1) (4G/5G insertion/deletion) polymorphisms with MI in the Pakistani population. In MI patients the genotype distribution of the PAI-1 gene was not found to be different when compared with the unaffected controls (P > 0.05, χ2 = 1.03). The risk allele 4G was also not associated with MI (P > 0.05, χ2 = 0.46, odds ratio (OR) = 1.1 (95% confidence interval (CI) = 0.84–1.43), P > 0.05). Similarly, the genotype frequencies of t-PA I/I, I/D and D/D were not different from the unaffected controls (P > 0.05, χ2 = 1.60), and the risk allele “I” was not found to be associated with MI (P > 0.05, χ2 = 1.35, OR = 0.86 (95% CI = 0.66–1.11), P > 0.05). However, when the data were distributed along the lines of gender a significant association of the 4G/4G PAI-1 genotype was observed with only the female MI patients (P < 0.05, z-test = 2.21). When the combined genotypes of both the polymorphisms were analyzed, a significant association of MI was observed with the homozygous DD/4G4G genotype (P < 0.01, z-test = 2.61), which was specifically because of the female samples (P = 0.01, z-test = 2.53). In addition smoking (P < 0.001, χ2 = 13.52, OR = 3.45 (95% CI = 1.77–6.94)), diabetes (P < 0.001, χ2 = 22.45, OR = 8.89 (95% CI = 2.96–29.95)), hypertension (OR = 7.76 (95% CI = 2.88–22.68), P < 0.001) family history (P < 0.001, χ2 = 13.72, OR = 3.7 (95% CI = 1.71–8.18)) and lower HDL levels (P < 0.05) were found to be significantly associated with the disease. In conclusion the PAI-1 gene polymorphism was found to have a gender specific role in the female MI patients.
KeywordsMyocardial infarction Tissue-plasminogen activator Plasminogen activator inhibitor Coronary artery disease
We would like to thank all the subjects for donating their blood. This work was financially supported by Grant No. 934 from the Higher Education Commission of Pakistan, awarded to RQ. Part of this work was supported by Shifa College of Medicine through a core grant.
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