Association Of Endothelial Lipase Gene Polymorphisms With Coronary Heart Disease

Coronary atherosclerotic heart disease, or coronary heart disease(CHD) for short, is a heart disease caused by coronary atherosclerotic lesions. Its clinical manifestation is a series of myocardial ischemia and hypoxia conditions,such as chest pain, palpitations, angina pectoris, myocardial infarction. In 2005, coronary heart disease has become the third death cause for urban residents in C hina, while in 2020, both in developed and developing countries, coronary heart disease will be the primary disease burden. Endothelial lipase(EL) is encoded by endothelial lipase gene(LIPG) which is located on chromosome 18q21.1. EL plays a vital role in plasma levels of HDL-C and its metabolism; In addition, it is also closely related with inflammatory response, insulin resistance, and obesity. Thus, EL may have an influence on atherosclerosis and coronary heart disease. Although studies of the association between LIPG polymorphisms and CHD have been conducted in Caucasian, Japanese, Chinese Han and Uygur populations, the results are conflicting and controversial. Hence, the association of LIPG polymorphisms with CHD needed to be explored further.Objective The purpose of this study was to confirm the association of LIPG variants with CHD, and investigated whether LIPG interacted with environmental factors to influence the risk of C HD in Chinese Han population.Methods 754 cases and 760 controls were recruited from the General Hospital of Jilin Chemical Group Corporation and the First Hospital of Jilin University. Medical record and medical examination report were used to collect study subjects’ information. Genotyping the four single nucleotide polymorphisms(SNPs) was conducted by MALDI-TOF mass spectrometry. The C hi-square test was used to check if genotype distributions were in Hardy-Weinberg equilibrium(HWE) and if allele IV frequencies and genotype distributions were significantly different between cases and controls. Estimation of Linkage disequilibrium(LD) of 4 SNPs in LIPG(D’ and r2 represent the degree of LD) was analyzed by haploview 4.2 so ftware. Inheritance model analysis and haplotype analysis were analyzed using SNPStats program. The logistic regression analysis was used to detect gene-environment interaction on the risk of C HD.Results(1)754 CHD patients and 760 controls were recruited into this study. The distributions of age and sex in cases were not significantly different from that of controls(P>0.05). The levels of TC, TG, LDL-C, GLU, SBP, and DBP were higher in CHD patients compared to controls, but the HDL-C level was higher in co ntrols compared to CHD patients(C HD patients: 1.15±0.33, control: 1.31±0.25).(2)In case group,there were 378 smokers(50.1%), 107 drinkers(14.2%), 444 hypertension patients(58.9%), and 110 diabetes mellitus patients(14.6%); In controls, there were 88 smokers(11.6%) and 55 drinkers(7.2%). There was no hypertension and diabetes mellitus patient in control group.(3)The genotype distributions of the four LIPG SNPs were conformed to HWE(P>0.05).(4)No significant differences were observed in allele frequencies and genotype distributions of the four LIPG SNPs between cases and controls(P>0.05).(5)The haplotypes of AC, TC, CA, CAC, TAA, CAC, ATC, ACA, CATC, CACC and TAC A were significantly associated with CHD(P<0.05).(6)No significant interaction was observed between LIPG polymorphisms and hypertension, diabetes mellitus, smoking, or alcohol drinking on the risk of CHD(P>0.05).(7)In all subjects and cases, SNP rs3786248 was significantly associated with plasma levels of TC and LDL-C(P<0.05). Similar results were obtained from SNP rs9958734 and rs3786247(P<0.05).Conclusion(1)Variants in LIPG were not found to be associated with CHD.(2)The haplotypes of AC(rs3786248, rs3786247), TC(rs9958734, rs3786247), CA(rs9958734, rs3786247), CAC(rs2000813, rs3786248, rs9958734), TAA(rs2000813, rs3786248, rs3786247), CAC(rs2000813, rs3786248, rs3786247), ATC(rs3786248, rs9958734, rs3786247), ACA(rs3786248, rs9958734, rs3786247), CATC, CACC and TACA were associated with the decreased risk of C HD.(3)Our study did not demonstrate that LIPG variants interact with environmental factors to affect the susceptibility of individuals to CHD.(4)SNP rs3786248, rs9958734 and rs3786247 might influence serum TC and LDL-C levels.