Genome Association Study At Chromosome13and Their Susceptibility For Coronary Heart Disease In A Chinese Population

BackgroundCoronary heart disease (CHD) is one of the most important health problems worldwide causing the high rate of mortality and morbidity in both developed and developing countries. Epidemiologic studies have revealed some risk factors for CHD, such as increasing age, gender, hypertension, dyslipidemia. obesity, diabetes, and smoking. However, although exposed to the similar conditions, some populations are more susceptible to CHD than others. These years, studies on premature coronary artery disease, twins and epidemiological surveys all find that there is a strong genetic factor underlying this disease.At present, genome-wide association studies (GWAS) has been widely used to identify regions on chromosomal which associated with complex disease. Many susceptibility genes for CHD have been discovered, some of which had been found in most of the nations, but the reports on chromosome13and CHD are seldom. Susceptibility genes for CHD on chromosome13q12,13q13.1,13q14.11,13q34were found in some populations but have not been replicated in Chinese subjects. For the purpose of testing genetic loci associated with CHD on chromosome13and verifying those susceptibility loci, a chromosome-wide scan was performed in CHD patients and controls in Shandong province of China. To our best knowledge, the presents study is the first study to describe the relationship between chromosome13and CHD in a Chinese population. Our current results will help to understand the genetic factors that affect the risk of cardiovascular disease in this Chinese population.ObjectiveTo research the association between chromosome13and CHD in a population from Shandong Province of China.Subjects and methodsThe case group consisted of156CHD patients, which had been confirmed by coronary angiography (CAG) in Qilu Hospital of Shandong University from May2007to October2007, including121males and35females, aged from17to61. The inclusion criteria were as follows:(1) clinical presentation;(2) electrocardiogram (ECG) changes are in line with WHO diagnostic criteria for the development of coronary heart disease;(3) CAG showed that at least one coronary artery stenosis^50%;(4) exclusion of familial hypercholesterolemia, severe liver and kidney diseases. The control group consisted of1000healthy blood donors selected from the Blood Center of Shandong Province, including702males and298females, aged from17to55. The selection criterion was previously healthy. A total of14microsatellite markers on chromosome13spaced at approximate10cM were used in screening of two separated DNA pool samples consisting of156CHD cases and1000normal controls. Statistic analysis was performed by CLUMP software to compare the difference in allele frequency of each locus between the two pooled samples.Results1. The genotypes of all the14microsatellite markers on chromosome13were polymorphic in the cases and controls, and the numbers of alleles on these loci were ranged from4to15.2. We used CLUMP software for comparing the differences in allele frequency of each locus between the two groups and contrasted the distribution of the alleles. The significant statistic differences between allele frequencies of cases and controls at markers D13S263(X2=15.412620, P=0.014985) and D13S156(X2=14.152888, P0.003996) were found. There were10alleles at D13S263(150,156,158,160,162, 164,166,168,170, and172bp), in which the156bp allele frequency in the cases was significantly higher than that of the controls, while the164bp allele frequency in the cases was significantly lower than that of the controls; There were7alleles at D13S156,(278,280,282,284,286.288, and290bp). in which the290bp allele frequency in the cases was significantly higher than that of the controls. The differences of allele frequencies in both patient and control groups for D13S263(13q14.11) and D13S156(13q22.1) were all statistically significant (P<0.05).3. The allele frequency of the remaining12loci had no significant statistic difference between the cases and controls, including D13S175(x2=4.377862, P=0.310689), D13S217(X2=.159211, P=0.063936), D13S171(X2=0.345870, P=0.935065), D13S158(X2=7.306865, P=0.106895), D13S285(X2=4.766732, P=0.856144). Therefore, they did not show any association with CHD.ConclusionsThe data provide support for the existence of13q14.11and13q22.1on chromosome13being associated with CHD in this population, and the susceptibility genes around these regions need to be further studied.