| Objective Coronary heart disease (CHD) is a complex disease due to genetic variantssynergetic action with external factors. The genetic factors are complex, and there arelots of genes associated with CHD. The interactions of genes, along withenvironmental factors, can increase the prevelance of CHD. Genetic factors play animportant role in the process of CHD. Hence the association studies on geneticvariants are being focued on. Genetic studies on CHD previously focused onidentifying these candidate genes on lipid pathway, blood pressure pathway andimflammation pathway. However, coagulation mechanism, aging and immunitymechanism also participate in the process of atherosclerosis. Therefore the candidategenes associated with these mechanisms may increase the prevalence of CHD. Ourstudy chose TFPI and FoxO as candidate genes, and to evaluate the associationbetween the gene variants and CHD.Coronary heart disease (CHD) is due to genetic factors synergetic action withenviornemtal factors. We should pay attention to the role of environmental factos.Prvious clinical studies emphasized that it was elderly, male and multi-factors disease,ingoring the gender difference also as an important risk factor. Moreover we shouldalso prevent and cure CHD according to different age stages of subjects. Hence ourresearch was to determine the prevalence of conventional risk factors and analyze thecharacteristics of coronary lesion on CHD among different sex populations.Methods3765CHD cases were collected from the general Hospital of PLA inBeijing from2009to2010(2661men,1104women). All the CHD patients enrolledin our study were made a definite diagnosis by angiography. We collected the clinicaldata and angiographic data of CHD patients. After stratification according to thepatients' age and gender, Logistic analysis was used to evaluate the prevalence ofconventional risk factors and analyze the feature of coronary lesion in CHD. We selected808CHD patients who had lived more than20years in Beijing or wasborn in Beijing.829controls with age-and sex-matched were from the same region.Population2was from Harbin region, including463cases also verified CHD withcoronary angiography and458controls with age-and sex-matched.The investigated SNPs were: rs2755209, rs2721072, rs4325427and rs17592371ofFoxO1; rs768023and rs126816of FoxO3; rs7586970, rs6434222and rs10153820ofTFPI. We testified whether these gene variants attributed to CHD.Result1.Characteristics of traditional risk factors and coronary lesion on CoronaryHeart Disease among different sex populations1.1the female patients took account for29.3%; More than two risk factors and moreadvancing onset age were common in women CHD patients.1.2Logistic analysis suggest that smoking be harmful for men (ORm=9.270,95%CI7.682-11.187, Pm＜0.001), diabetes mellitus enhance the prevalence of CHD forwomen (ORm=2.05,95%CI1.49-2.81, Pm＜0.001), hyperlipidemia increase the riskfor women(ORm=1.40,95%CI1.06-1.86, Pm=0.02).But hypertension be notassociated with CHD due to gender difference(ORm=0.88,95%CI0.65-1.21, Pm=0.44). Excluding the impact of cofactor-age, smoking, diabetes mellitus andhyperlipidemia are still associated with CHD.1.3We analyzed the association between risk factors and gender after stratification byage, according to men as reference, ORsmoking=0.11(0.09-0.13),ORDM=2.00(1.72-2.33),ORhyperlipidemia=1.17(1.01-1.36),ORhypertension=0.98(0.84-1.15).1.4The association between the characteristics of coronary lesions and gender suggestthat the degree of coronary lesions was more severe in male. Excluding the impact ofcofactor-age, coronary lesions were still associated with gender in CHD. Afterstratification by age, female patients had more coronary vessel injured and moresevere coronary artery lesion in the elder. Different from female, there was no changein characteristics of coronary lesion with different age stages for male. 2. Genetic research on CHD2.1we selected the6SNPs of FoxO1and FoxO3. First we validated in population onefrom Beijing, there was no statistical significance for investigated6SNPs of FoxObetween case and control in population one (p＞0.05). Then the association study wasrepeated in the second population from Harbin. The data suggest that there were alsono statistical difference in population two. After combining the two subjects fromBeijing and Harbin, the data showed that these SNPs did not necessarily dispose forCHD (p＞0.05). Subgroup analyzed according to different genders and the pastmedical history of smoking, hyperlipidemia, diabetes mellitus and hypertension, weexplored further that the variants of FoxO1/FoxO3may not be linked to CHD (p＞0.05).2.2we selected the3SNPs of TFPI. First we validated in population one from Beijing,there was no statistical significance for rs10153820of TFPI between case and controlin population one (p＞0.05). There were statistically significant in frequencies ofrs7586970and rs6434222(rs7586970: OR=0.83,95%CI0.70-0.99; rs6434222:OR=1.26,95%CI1.05-1.52). After Bonferroni step-down method for multiplecomparison correction, rs6434222still remained significant (P=0.012). Then the sameassociation study was repeated in the second population from Harbin. After subgroupanalysis, we did not explore further significant outcome.2.3We compared the contributions of environmental factors (smoking, hypertension,diabetes mellitus and hyperlipidemia) and inherit factors (3SNPs of TFPI) to CHD.The data suggest that environmental factors be more likely to contribute to theprevelance of CHD compared with inherit factors.Conclusion1.1due to different genders, prevalence of risk factors and characteristicsof coronary lesion are different at different age stages. Diabetes mellitus andhyperlipidemia seemed to impact on women more, while smoking affected men moresignificantly.2.2the variants of FoxO1/FoxO3may not increase the prevalence of CVD in HanChinese population from north. However TFPI polymorphism may be responsible for risk of ACS in Han Chinese. Environmental factors be more likely to contribute to theprevelance of CHD compared with inherit factors. |
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