Association Between Polymorphism Of Chloride Channel-6 Gene And Coronary Heart Disease

Objective To explore single nucleotide polymorphism of rs3737964,3737965 of chloride channel-6 (CLC-6) gene and to ascertain the relationship between the polymorphi- sm of CLCN-6 rs3737964,rs3737965 gene and coronary heart disease (CHD) in Chinese han population.Methods 1193 CHD patients and 1200 age and sex frequency matched control su- bjects were collected. The epidemiology data such as sex, age, vocational history, life style (smoking, drinking, physical activity and so on) and social-psychic factors were gathered by mended Inter-heart questionnaire interview, and blood samples of all subjects were collect- ed. Then the CLC rs3737964, rs3737965 polymorphism of extracted deoxyribonucleic acid (DNA) was genotyped by real-time quantitative polymerase chain reaction (real-time Q- PCR) method. Then, the genetypes were analyzed by software of SDS 2.2.1. Furthermore, the association between CLC-6 rs3737964, rs3737965 polymorphism and CHD was analy- zed by SPSS 10.0 software.Results Frequencies of T and C alleles of chloride channel-6 rs3737964 were 10.4% and 89.6% in the all investigated population respectively,the frequencies of T and C alleles of rs3737965 were 9.3% and 90.7% respectively,the observed and expected genotypes we- re in agreement with the predicted Hardy-Weinberg equilibrium values(P=0.178 and 0.202. The frequency distribution of TT and CC genotype had no significantly difference between the coronary heart disease group and the control group(P>0.05), the frequency distribution of TT genotype in the coronary heart disease group is 0.6%, in the mean time the control group is 0.9%. CC genotype in the coronary heart disease group is 83%, in the mean time the control group is 81.3%. This increased risk of coronary heart disease was not significant when before adjust risk factors in unconditional Logistic regression analysis (OR=0.688, 0.9 respectively P>0.05, the association between the genotypes and the coronary heart disease wasn't revealed after adjusted the risk factors. The frequencies of TT genotype of rs373796 4 were significantly higher in the CHD group (2.3%) than the control group(1.0). The TT genotype had a significantly increased risk of CHD(OR=2.925, 95%CI=1.168- 4.063,P=0.0163) compared with the CC genotype, this increased risk was still significant when adjusted for the coronary heart disease risk factors such as age, sex, smoking, drinking, body mass index, history of hypertension and diabetes mellitus, and the family history of coronary heart disease. The stratified analysis implied that in the population of smoking, male and over age of 60, the frequencies of TT genotype of rs3737964 had significant relationship with the morbidity of CHD. The population which that over age of 60 whose OR=2.197, 95% CI=0.888-5.435, P=0.0887, and after adjusted was OR=3.597, 95%CI=1.1 91-10.858, P=0.022. The result implied that the TT genotype in age which over age of 60 were prone to suffer CHD. The increased risk was significantly higher in TT genotype of male before and after adjusted, OR=2.851, 3.669; 95%CI=1.261-6.447, 1.401 -9.608; P= 0.0119, 0.0081 respectively. Which implied the TT genotype of male were more easily to suffer CHD. OR=2.501, 95% CI =0.902-6.932, P=0.0780 in smoking populat- ion before adjusted. The increased risk was significant in TT genotype when adjusted for sex, age, drinking, excise, history of hypertension and diabetes mellitus and the family history of CHD, OR=3.187, 95%CI=1.038-9.787, P=0.0429, which suggested that the TT genotype in smoking were prone to suffer CHD.Conclusion: The result suggest that the chloride channel-6 rs3737964 polymorphism may be associated with the CHD, especially with the TT genotype in age who over age of 60, smoking and male. The polymorphism of chloride channel-6 rs3737964 appears to be a useful genetic marker of CHD. The polymorphism of chloride channel-6 rs3737965 is not related with CHD.