The Relationship Between CAG Polymorphisms Of Androgen Receptor Gene And Acute Myocardial Infarction In Men

Objective:As we all know, age, gender, family history, hypertension, dyslipidemia, abnormal glucose metabolism, smoking, overweight and obesity, lack of exercise and psychological stress become the major risk factors for coronary heart disease. The male gender has become an independent risk factor for cardiovascular disease. In recent years, people become increasingly concerned about the role of androgen in the pathogenesis of cardiovascular disease in men. At present, the relationship between androgen and cardiovascular disease in men is not very clear. The effect of androgen is mediated by androgen receptor (AR),which has a polymorphic CAG repeat in exon1.The number of CAG repeats is inversely related to the transcription activity of AR. We aim to study the CAG polymorphisms of androgen receptor gene, and to explore the relationship between CAG polymorphisms of androgen receptor gene and acute myocardial infarction in different gender. Our study may provide a new perspective for clarifying the role of androgens on the cardiovascular system.Methods:112acute myocardial infarction patients of men aged from31to87,who were collected at the Cardiology of the Second Hospital of Tianjin Medical University hospital, as the male patient group.118healthy men aged from39to93, who were collected at the department of Health Care of the Second Hospital of Tianjin Medical University hospital, as the male control group.At the same time,58acute myocardial infarction patients of women aged from36to84as the female patient group.49healthy women aged from34to80as the female control group. The next morning, all selected objects were collected venous blood2mL of sodium citrate anticoagulant.The blood frozen at-80°C.For all selected objects, lipids, liver function, kidney function, fasting glucose and other clinical and biochemical indicators were recorded.Medical history including gender, age, height, weight, smoking, hypertension, diabetes mellitus(DM), family history of CAD and so on were taken and body mass index (BMI) was measured. Whole blood genomic DNA was extracted in accordance with the blood genomic DNA extraction kit. The length of CAG repeats in the peripheral blood AR gene was amplificated through polymerase chain reaction (PCR),and the PCR product was detected by1.5%agarose gel electrophoresis. Nested PCR reaction products were purified, recovered and sequenced in Beijing Liu he Genomics Institute of Science and Technology.Results:(1)For the male AMI patients and the male controls, the numbers of CAG repeats ranged from12-33,with mean values23.09±3.520and20.33±3.654,respectively.There were statistically significant differences between two groups. Men with CAG repeats length of23or longer may be in high risk of AMI(odds ratio,4.479;95%CI2.564-7.824, P<0.001),compared with men with CAG repeats length shorter than23. Men with CAG repeats length of22-23or longer than24may be in high risk of AMI(odds ratio,2.236and4.269;95%CI1.611-3.104and2.144-8.500, P<0.001),compared with men with CAG repeats length shorter than22.(2) In AMI as the dependent variable, the CAG repeat length (≥23and<23), smoking, high blood pressure, fasting glucose, HDL-C as independent variables, Logistic regression analysis showed that CAG repeat length, smoking, high blood pressure, fasting blood glucose were risk factors, and HDL-C was protective factors for male AMI.(3). For the female AMI patients and the female controls, the numbers of CAG repeats ranged from16-32,with mean values23.09±3.585and22.51±2.591,respectively.There were no statistically significant differences between two groups(t=0.996, P=0.321).Conclution:(1) Androgen receptor gene CAG repeats showed polymorphisms in Chinese people.(2) The androgen receptor gene CAG repeat length of the male AMI group is greater than the male control group. The CAG repeat length, smoking, high blood pressure, fasting blood glucose were risk factors, and HDL-C was protective factors for male AMI.(3) There may be no relevant between androgen receptor gene CAG repeat length and AMI in women.