Study On The Association Between The Environment Factors And IL-17 Genetic Polymorphisms And Risk Of Developing Coronary Heart Disease

[Background and purpose] Coronary heart disease (CAD), also known as coronary atherosclerotic heart disease, is caused by a coronary artery atherosclerotic lesion in the vascular lumen stenosis or obstruction, led to myocardial ischemia, hypoxia and necrosis caused by heart disease. Location of coronary heart disease may also include the category of vascular lumen stenosis caused by inflammation, embolism etc. At present, WHO divided the coronary heart disease into 5 types:no symptoms of myocardial ischemia, angina, myocardial infarction, ischemic heart failure and sudden death. In clinical, coronary heart disease were often divided into stable coronary artery disease and acute coronary syndrome. Coronary heart disease is the most important causes of death disease in Western countries. Atherosclerosis in coronary artery, brain and peripheral blood vessels have different clinical manifestations, such as myocardial infarction, stroke and cardiovascular death. In the past few decades, people for the understanding of the pathophysiology of cardiovascular disease have great developed, and understand the process of atherosclerosis in inflammation, and the inflammatory process is the main factor. In addition, some subclinical inflammation, such as rheumatoid arthritis, diabetes, is also considered a strong risk factor for CAD.CAD has a high morbidity and mortality, the disease bring to population health serious effect and lead to heavy social and economic burden. The pathogenesis of CAD has not been fully elucidated; studies showed, including environmental, gene and other factors have a close relation with the occurrence and development of CAD. In industrialized countries, CAD is still the most important fatal disease. Each of the 6 cases in the United States in 2010, one cases of death is caused by CAD. In the UK, the disease burden of coronary heart disease is enormous, coronary heart disease is the leading cause of death in 2012 of British women’s first (28%), but the leading cause of death for men (32%) is tumor. At the same time, the distribution of death caused by coronary heart disease in the UK is also inconsistent; the mortality rate is the highest in Scotland and Northern England. According to the National Health Service center of England data showed that in 2012-2013 years, the economic costs of coronary heart disease produce up to 680 million Euros, a heavy burden to the whole society. In China, the distribution of coronary heart disease epidemic has its own characteristics, mainly for the incidence of coronary heart disease and death between different regions and the distribution is consistent, showing the characteristics of northern regions the incidence is higher, the southern region lower onset; men than women with higher coronary heart disease morbidity and mortality, the incidence of urban higher than in rural areas. With the increasing of people’s living standard, the incidence of coronary heart disease increased year by year, and has become a serious impact on the life and health of the population problems.The pathogenesis of coronary heart disease is complex, involving the interaction of many risk factors. Traditional risk factors, such as:smoking, hypertension, diabetes, high blood lipids, has been studied clearly. In recent years, the study found some patients with coronary heart disease had traditional risk factors for the prevalence of different. Therefore, the reoccurrence of coronary heart disease on risk factors is important and comprehensive understanding has very important meaning and function. Single nucleotide polymorphisms (SNPs) is the cause of disease is different between different individual susceptibility to one of the important reasons of IL-17A and IL-17F is an important proinflammatory cytokines, and were expressed in a variety of cells. IL-17A and IL-17F can induce the expression of a variety of cytokines, including the tumor necrosis factor alpha and interleukin 1, interleukin 6, interleukin-18, macrophage colony, chemokines, antibacterial peptides, fibroblast of nuclear factor kB, and can promote tissue invasion and tissue destruction. IL-17A and IL-17F genetic polymorphisms can affect the change of DNA sequences, including the lack of a single nucleotide bases, inserts, replaced, and most of the bases are CC base. Gene tubing can occur in any site in the genome, including gene exon and intron, promoter, enhancer, and the interval between two genes, and single nucleotide polymorphism susceptibility to humans from all aspects. This study carried out a case-control study, and investigated the association between environmental factors and IL-17A(rs2275913å'Œrs3819025) and IL-17F (rs3748067) polymorphisms and risk of developing coronary artery disease, and analyzed the interaction between genetic factors and environmental factors, and provide scientific basis for the prevention and control of the disease.Material and methods:Some epidemiological studies showed age, overweight or obese and risk of some social and psychological factors in patients with coronary heart disease with uncertain conclusions. The inconsistency of the results of these studies may be factors in reaction to the design of epidemiology of sample selection and bias problem, the object of study of individual differences, and exposure factors between different countries or regions.Therefore, to carry out research on risk factors of coronary heart disease in the distribution of different regions, it has very important guiding role for the region of coronary heart disease prevention and treatment.[Materials and methods] this study used a case-control analysis method to carry out the related risk factors of coronary heart disease. We included in our hospital of 446 patients with coronary heart disease as the research object, and healthy people in our hospital physical examination center in the same period of physical examination in 454 cases as control. Collected and collated the case group and the control group of general information, including age, gender, educational level, and two groups of subject’s history, eating habits and other information, collected blood samples from the object of study for detection of serum lipid levels. By face to face questionnaire survey information collection, and extract the respondents peripheral venous blood of 5 ml, using ethylenediamine tetraacetic acid dipotassium antithrombotic treatment (EDTA-K2), put in-20 cryogenic refrigerator preservation under test will EDTA-K2 anticoagulation in acquisition of peripheral venous blood vessels 5 ml, according to the genome of blood extraction kit steps for the extraction of blood samples from the genome. IL-17A(rs2275913å'Œ rs3819025) and IL-17F (rs3748067) polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. IL-17A(rs2275913 å'Œ rs3819025) and IL-17F (rs3748067) restriction enzymes. After the reaction, a product will take 5 mu 1 enzyme and 1 mu 1 bromophenol blue on the sample buffer blending for preliminary analysis, placed on a 3% agarose gel electrophoresis, and observed under UV light. Using SPSS 19.0 (version 19.0, SPSS Inc., Chicago, IL, USA) statistical analysis, all the statistical tests are bilateral inspection, and a less than 0.05 was considered significant difference. Using single factor and multiple factors unconditioned logistic regression analysis of environmental risk factors and IL-17A(rs2275913 å'Œ rs3819025) and IL-17F (rs3748067) and the correlation between coronary heart disease susceptibility.[Results]1. Comparative analysis of general data:General data of the comparative analysis:the case group and control group in the gender live body mass index (BMI) history of diabetes exercise Serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) smoking and drinking milk and its products fruits and caffeine intake differences between the two groups have statistical significance.2. Single factor of Logistic regression analysis showed that in general data results, gender OR=2.30,95%CI,1.71-3.10; age, OR=1.7995%CI 1.36-2.36; residence 1.39,95%CI 1.06-1.83; BMI index 3.72,95%CI 2.80-4.95; waist hip ratio of 5.32,95% CI is 3.94-7.19; the risk of diabetes OR=2.10,95%CI 1.51-2.93; hypertension is 2.47,95%CI is 1.78-3.44; the protective factors for the exercise of the risk of coronary heart disease; coronary heart disease risk for TC OR=1.01,95%CI 1.01-1.02; TG 1.03,95%CI 1.02-1.04; LDL-C is 1.01,95%CI is 1.01-1.02; HDL-C is a protective factor for smoking; Smoking was risk of coronary heart disease, OR=1.90,95%CI 1.46-2.48; milk and dairy products and fruit intake for coronary heart disease are found as a protective factor, ORs were 0.49 (95%CI 0.24-0.97),0.44 (95%CI 0.22-0.87) and 0.40 (95%CI 0.25-0.66), caffeine intake for coronary heart disease were risk factors OR=2.26,95%CI 1.47-3.47.3. Multivariate regression analysis results:multivariate analysis and single factor analysis results are similar, but the sex and the single factor analysis result showed the incidence of women on the contrary, OR=0.44 95%CI,0.30-0.65; age, OR=1.94 95%CI 1.34-2.81; BMI index is 4.45,95%CI is 3.07-6.46; waist to hip ratio 4.87, 95%CI 3.35-7.10; the risk of diabetes OR=2.08,95%CI 1.32-3.28; hypertension was 1.70,95%CI 1.14-2.54; TC was 1.02,95%CI 1.01-1.02; TG 1.04,95%CI 1.03-1.05; LDL-C 1.02,95%CI 1.01-1.02; HDL-C for the protection factors, OR=0.89,95%CI to 0.86-0.92; the risk of smoking was 1.90,95%CI was 1.46-2.48; smoking years 1.88,95%CI 1.07-3.28; years of drinking OR=2.10,95%CI 1.05-4.21; caffeine intake was 2.6195%CI,1.47-4.63; intake of fruits and grains for the protection of the Protective factors, the OR values were 0.29 (95%CI 0.15-0.58),0.46 (95%CI 0.25-0.86).4. IL-17 rs2275913 (chi-square=2.08, P=0.149) and r3819025 (chi-square=0.03, P=0.03) in the case group distribution accord with Hardy-Weinberg laws of balance, but IL-17 rs3748067 (chi-square=35.40, P< 0.001) do not conform to the Hardy Weinberg equilibrium. In the control group, IL-17 rs2275913 (chi-square=4.19, P=0.041), r3819025 (chi-square=5.65, P=5.65) and rs3748067 (chi-square=12.52, P=12.52) gene frequency distribution does not conform to the Hardy Weinberg equilibrium.5. IL-17 rs2275913 gene GG, GA and AA genotype, respectively,181 (40.58%), 200 (44.84%) and 65 (14.57%), in the control group, IL-17 rs2275913 gene GG, GA and AA genotype, respectively,210 (46.26%),208 (45.81%) and 36 cases (7.93%). The case group and the control group of IL-17 rs2275913 gene GG, GA and AA genotype distribution difference was statistically significant (chi-square= 10.564, P=10.564).6. In co-dominant model, carrying IL-17 rs2275913 GA and AA genotype individuals compared to carry GG genotype individuals, the risk of coronary heart disease has increased 1.878 times and 2.095 times respectively, the corresponding OR 1.878 (95% CI) (1.196-2.948) and 2.095 (1.332 3.296) times. In recessive models, carrying the AA genotype individuals compared with the individual carrying+GA genotype GG, a 1.981-fold increased risk of coronary heart disease, corresponding the OR was 1.260 (95% CI) (0.9681.641) times, but no association between IL-17 r3819025 and rs3748067 gene polymorphism and coronary heart disease risk.7. Multiple factors regression analysis found that carry IL-17 rs2275913 gene of AA genotype and GA genotype individuals compared with the individual carrying type GG genotype, CHD risk of significant increased by 2.286 times and 2.286 times of the corresponding adjusted OR (95% CI) 2.286 (1.2754.100) and 2.133 (1.197 3.799). In recessive models, carrying IL-17 rs2275913 AA genotype individuals compared with carrying GG+GA genotype, the risk of coronary heart disease has increased 2.204 times, corresponding the OR(95% CI) was 2.204(1.270 3.826).8. The study found that IL-17 rs2275913 relevant relationship between gene polymorphisms arid hypertension family history, Spearman correlation coefficient is 0.075, the corresponding P value is 0.025.[Conclusions] this research for coronary heart disease incidence and risk in the past and all kinds of risk factors between the correlation research conclusions is consistent, patient’s age, gender, medical history, physical activity, smoking and drinking, overweight and obesity, and diet and other factors had relationships with coronary heart disease occurrence and development. LI-17 rs2275913 gene polymorphism can increase the risk of coronary heart disease.