Study On The Relationships Between Peroxisome Proliferator-Activated Receptor γ2 Gene Polymorphisms And Haplotypes And Myocardial Infarction

【Objective】Activation of peroxisome proliferator-activated receptor-γ2 improves the sensitivity of insulin and exerts anti-atherosclerotic, anti-inflammatory, anti-oxidative and anti-fibrotic which are generally considered to beneficial for myocardial infarction (MI).Some studies demonstrated that the C-689 T substitution in the promoter of PPARγ2 decreased the activity of the receptor. The study was to investigate the association between C-689T polymorphism in the PPARγ2 promoter and MI.【Methods】This is a case-controlled study, which enrolled 194 subjects with MI (cases) and 693 subjects without MI (controls) in Wuhan Han people. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the C-689 T substitution. We detected fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) by using the method of biochemistry; measured anthropometrical parameters such as waist circumference, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP); required for these information of age, smoking, drink, and physical activities in a standard questionnaire. Hardy-Weinberg law was used to detect population representive and logistic regression analyses were used to investigate the association between C-689T polymorphism and MI.【Results】The CC,CT, and TT genotype frequencies of C-689T polymorphism were 0.881,0.119,and 0.000 in cases and 0.931,0.066,and 0.003 in controls, respectively (CC vs. CT+TT, P=0.025). The -689T allele was an independent risk factor for MI (OR=2.125, 95%CI: 1.206-3.744, P=0.009) after adjusting for age,sex,waist circumference,body weight, BMI, smoking, drink, physical activities, SBP, DBP, FBG, TC, and TG level. The -689T allele carriers had significantly higher TC level than noncarriers (5.05±1.16 vs. 4.78±1.05 mmol/L, P=0.004).【Conclusion】PPARγ2 gene C-689T polymorphism is associated with an increased risk of MI. 【Objective】There were many studies that demonstrate PPARγ2 gene Pro12Ala polymorphism was associated with myocardial infarction (MI). Recently it was reported that PPARγ2 promoter C-689T polymorphism was related to lower receptor activity and metabolic syndrome. As it is well known that MI and metabolic syndrome have common pathogeneses, and it is more suitable to investigate the association between complicated gene diseases and heredity in haplotype analyses. MI is a kind of complicated gene disease, the study was to investigate the association between PPARγ2 gene haplotypes (including Pro12Ala and C-689T polymorphisms) and MI.【Methods】This is a case-controlled study, which enrolled 194 subjects with MI (cases) and 693 subjects without MI (controls) in Wuhan Han people. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine Pro12Ala and C-689T polymorphisms. We detected fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) by using the method of biochemistry; measured anthropometrical parameters such as waist circumference, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP); required for these information of age, smoking, drink, and physical activities in a standard questionnaire. Hardy-Weinberg law was used to detect population representive, linkage disequilibrium law was used to detect linkage strength, logistic regression analyses were used to investigate the associations between the two polymorphisms and MI, and haplotype analyses was used to the associations between haplotypes and MI.【Results】The Pro12Pro,Pro12Ala, and Ala12Ala genotype frequencies of Pro12Ala polymorphism were 0.892,0.108,and 0.000 in cases and 0.929,0.068,and 0.003 in controls, respectively (CC vs. CT+TT, P=0.134).The CC,CT, and TT genotype frequencies of C-689T polymorphism were 0.881,0.119,and 0.000 in cases and 0.931,0.066,and 0.003 in controls, respectively (CC vs. CT+TT, P=0.025). Hardy-Weinberg law demonstrated the population had population representive, linkage disequilibrium analyses deplored Pro12Ala and C-689T polymorphisms had strong linkage disequilibrium (D'=0.840).In single analysis, Pro12Ala polymorphism was not a significant risk factor for MI ( OR=1.595,95%CI :0.932-2.732,P=0.089),the -689T allele was an independent risk factor for MI (OR=2.125, 95%CI: 1.206-3.744, P=0.009) after adjusting for age , sex , waist circumference,body weight, BMI, smoking, drink, physical activities, SBP, DBP, FBG, TC, and TG level. In haplotype analyses, Ala-T haplotype was a significant risk factor for MI(OR=1.785, 95%CI: 1.033-3.085, P=0.036).【Conclusion】PPARγ2 gene Ala-T haplotype is associated with an increased risk of MI.