The Relationship Between TLR4Gene Polymorphism And Interaction Of Environmental Risk Factors And CHD

Objective:To analyze the risk factors for coronary heart disease (CHD). Through observationthe genotype and allele distribution of tag SNPs, we study the association between TLR4genepolymorphisms and disease susceptibility. The study also detected the gene-environmentinteraction between SNPs in TLR4and traditional risk factors of CHD.Methods:In this study, case-control study was used. A total of577patients with CHD wererecruited from a hospital of Jilin University between2009and2012.517controlsubjects were randomly selected from the persons who were through the routinecheckup as part of annual body examination during the same period. Methods ofquestionnaire and physical examination were used to collect useful information of thetwo groups, such as demographic information, medical information, medical historyand laboratory data. Then,5mL of fasting venous anticoagulant blood was collectedfrom CHD patients and controls in order to extract genomic DNA. Four SNPs ofrs1927907, rs1927911, rs11536879and rs11536889were selected from public SNPdata in TLR4, and Sequenom Mass-ARRAY system was used to detect the genotypesof the above SNPs. SPSS13.0software was used for statistical analysis.Results:1. Smoking was significant different between case group and control group（P＜0.05）,and the proportion of smoker in the case group (37.1%) was significantly higher thanthat in the control group (23.6%). While no significant difference was found in thedistribution of drinking between the two groups（P＞0.05）.2. The difference of overweight/obese individuals between case group and controlgroup was not statistically significan（tP＞0.05）. While the distribution of individualswith central obesity was significantly different between the two groups（P＜0.05）,and the proportion of central obese individuals (85.6%) in patients was significantly higher than that in healthy (50.4%).3. The difference of hypertension history between case group and control group wasstatistical significance（P＜0.05）, and there were more people having hypertensionhistory in the case group (56.1%) than control group (31.6%). Systolic blood pressurein the case group was significantly higher than that in the control group（P＜0.05）,while the difference of diastolic pressure between the two groups was not statisticallysignificant（P＞0.05）. The history of antihypertensive treatment between the twogroups was significantly different（P＜0.05）, and the proportion of persons havinghad experience of antihypertensive treatment in the case group (41.6%) wassignificantly higher than control group (23.3%).4. The difference of diabetes history between case group and control group wasstatistical significance（P＜0.05）, and there was more people having diabetes historyin the case group (23.8%) than control group (12.5%). And individuals with GLU≥6.1mmol/L in the case group (44.2%) was significantly higher than control group(18.4%)（P＜0.05）.5. Individuals with TC≥6.62mmol/L in the case group (8.9%) was significantly lowerthan control group (13.5%)（P＜0.05）. While the distribution of individuals with TG≥2.26mmol/L was not significantly differenence between the two groups（P＞0.05）.History of the lipid-lowering therapy was significant different between the two groups（P＜0.05）, and there was more people having lipid-lowering therapy in the casegroup (10.1%) than control group (2.3%).6. The genotype and allele distribution of the four SNPs (rs1927907, rs1927911,rs11536879and rs11536889) in TLR4gene were not significantly different betweencases and controls（P＞0.05）.7. The haplotype frequencies of the three SNPs (rs1927911, rs1927907andrs11536889) did not show any significantly different between case group and controlgroup（P＞0.05）.8. There were no interactions between tags SNPs (rs1927907, rs1927911, rs11536879and rs11536889) and the three environmental risk factors of CHD（P＞0.05）.Conclusions: 1. Smoking, central obesity, systolic blood pressure, hypertension, diabetes andfasting blood glucose might be risk factors for coronary heart disease. While drinking,overweight/obese, TG and diastolic blood pressure might not be associated with therisk of coronary heart disease.2. TLR4gene might not be the susceptibility gene of CHD in Chinese Han population.3. The haplotypes of three SNPs (CGC, CGG, TAG and TGG) might not be associatedwith the risk of coronary heart disease.4. There might be no interactions between tags SNPs (rs1927907, rs1927911,rs11536879and rs11536889) and the three environmental risk factors of CHD.