The Association Study Between The APOA5 Polymorphisms And Plasma Lipid Levels And The Severity Of Coronary Stenosis In Chinese Han Coronary Heart Disease Patients

Objective: The aim of the study was to investigate the possible effects of the APOA5 rs2075291,rs3135507 and rs662799 polymorphisms on plasma lipid levels and the severity of coronary stenosis in patients with coronary heart disease(CHD)in Chinese Han people.Methods: The inpatient who underwent coronary angiography for suspected CHD at the Department of Cardiology,the Affiliated Hospital of North Sichuan Medical College(Nanchong,China)were enrolled in the study between April 2014 and July 2015.CHD was diagnosed in the patients who had angiographic evidence of stenosis greater than 50% in at least one major coronary artery.Those with normal coronary arteries,coronary atherosclerosis or minimal stenosis(less than 50%)in any of the major coronary arteries were considered as CHD-free control subjects.Polymerase chain reaction-restriction fragment length polymorphism method was used to identify the genotypes of the rs2075291,rs3135507 and rs662799polymorphism for all the subjects.According to the physiology and biochemical examination,Demographic characteristics,such as hypertension,diabetes,body mass index(BMI),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),apolipoprotein B100(APOB100)and apolipoprotein AI(APOAI)of the subjects were collected,and TG/HDL-C,TC/HDL-C,LDL-C/HDL-C and APOB100/APOAI could be calculated.The severity ofcoronary stenosis was assessed by the Gensini scoring system,and the differences in lipid levels and Gensini scores were compared between genotypes.Results:1.Among the 476 subjects who were underwent the identification of the rs2075291 and rs3135507 polymorphisms,324 subjects were diagnosed with CHD by coronary angiography,including 204 meals and 120 females,mean age of CHD patients was(64.74 ± 9.42)for males and(64.55 ± 8.31)for females;the rest 152 subjects were incorporated into CHD-free controls,consist of 81 males and 71 females,mean age was(60.12 ± 12.41)and(59.30± 9.68).The CHD patients had higher prevalence of hypertension,TG,TC,APOB100,TG/HDL-C,TC/HDL-C,LDL-C/HDL-C and APOB100/APOAI,and lower HDL-C and APOAI than the controls(P<0.05 for all).The distribution of the rs2075291 polymorphisms in both CHD patients and the controls had highest prevalence of GG homozygotes,then GT genotype and there was no TT genotype found among the subjects who were successfully identified;the most common allele was G and rarely saw T allele in the frequency distribution.In the genotypic distribution of the rs3135507 polymorphism,GG genotype was the most frequently,followed by GA genotype,then AA homozygotes in both two groups,the allele of G exhibited extremely higher frequency compare with the minor A allele.The allele and genotype frequencies were similar between the CHD patients and the controls in both rs2075291 and rs3135507 polymorphisms.The subjects with the rs2075291 GT genotype had higher levels of TG,TG/HDL-C and TC/HDL-C,and lower levels of HDL-C and APOAI than the subjects with the GG genotype(P<0.05 for all)in controls.In CHD patients,those with thers2075291 GT genotype had higher levels of TG,TG/HDL-C and TC/HDL-C,and lower levels of HDL-C than the patients with the GG genotype(P<0.05 for all).Regarding the rs3135507 polymorphism,no significant differences in lipid levels were found between the genotypes in controls or in CHD patients.No significant differences in Gensini scores were detected between the genotypes of the rs2075291 or rs3135507 polymorphism.2.A total of 478 subjects were identified the genotypes of the rs662799 polymorphisms,of these subjects,325 subjects were diagnosed with CHD,while the rest 153 subjects were free of CHD and considered as the control group.The former were made up of 205 males(age:64.63 ± 9.51)and 120females(age:64.48 ± 8.30),the controls were included of 81 males(age:59.88± 12.58)and 72 females(age:59.14 ± 9.69).The genotype distribution of the rs662799 polymorphisms in CHD patient and controls,the TT genotype was the most common,then TC,the last was CC homozygotes.The T allele frequency distribution of the rs662799 was consistent with an usual observation compared with minor C allele.The carriers of the variant C allele had higher ratio of TG/HDL-C and lower levels of HDL-C than the subjects without this allele in CHD-free women(P<0.05 for both).In CHD patients,the C carriers had higher levels of TG and TG/HDL-C than the TT genotypes in men,and had higher levels of TG,TG/HDL-C,TC/HDL-C and APOB100/APOAI than the TT homozygotes in women(P<0.05 for all).The C allele was associated with higher prevalence of dyslipidemia and higher levels of Gensini scores only in women(P<0.05 for both).The prevalence of C allele or the C allele carriers increased orderly with the tertiles of the Gensini scores in women patients(P<0.05),but not in men patients.Multivariate linear regression analysis showed that the rs662799 polymorphismwas independently associated with the Gensini scores in women after adjustment for other potential CHD risk factors(Beta=0.157,95%CI:0.017-0.298,P=0.028)Conclusion: In Chinese Han population,The APOA5 rs2075291 polymorphism had significant association with higher TG level and lower HDL-C level,but no effects on the occurrence and the severity of CHD.Regarding the rs3135507 polymorphism,no significant differences in lipid levels and in the occurrence or the development of CHD were found..The APOA5 rs662799 polymorphism had significant effects on plasma lipid levels,and which is associated with the severity of CHD in women.