Association Of Deoxyribonuclease I And Apolipoprotein E Genetic Polymorphisms With Serum Lipid Levels And Coronary Artery Disease In Han Chinese

Background: DNASE1, the encoding gene of deoxyribonuclease I (DNase I), exhibits polymorphism (SNP A2317G) in exon 8 and a 56bp variable number of tandem repeat, designated as HumDN1 in intron 4. Several different ethnic population studies have revealed both A2317G and HumDN1 demonstrate genetic heterogeneity in worldwide distribution. Recently, G2317 allele was proposed as an independent risk factor for myocardial infarction in Japanese population.Methods: In the present study, we identified A2317G and HumDN1 genotypes in 402 unrelated healthy Han Chinese individuals. At the same time, the impact of different genotypes and diplotypes of DNase I on plasma lipids levels and fasting blood glucose was also illuminated. Polymerase chain reaction and restriction fragment length polymorphism were used for the detection of HumDN1 and A2317G polymorphism. Plasma glucose and lipids were measured in fasting state by biochemical methods.Results: Three genotypes of A2317G and 9 genotypes of HumDN1 were detected in Han Chinese population. Among them, the most predominant alleles were A2317 (frequency=53%) and HumDN1*3 (frequency=48%) respectively. Linkage disequilibrium between A2317G and HumDN1 was also observed (D'=0.717). Haplotype A-3, presentd in frequency of 46.5%, was most common. As for the influence of DNase I gene polymorphisms on lipids and glucose levels, no assocaiton was found between either genotypes or diplotypes and these parameters. (all P>0.05). Conclusions: Compared to other ethnic populations, Han Chinese had its own unique DNase I gene distribution characterisrics. Results obtained in this study could be used for anthropological investigation, probing into relations between DNase I gene and diseases.Part 2 Association of deoxyribonuclease I genetic polymorphisms with acute myocardial infarction in Han ChineseBackground: Deoxyribonuclease I gene exhibits polymorphisms, including a single nucleotide polymorphism (A2317G) and a 56bp variable number of tandem repeat, designated as HumDN1. G2317 was regarded as an independent risk factor for Japanese myocardial infarction patients.Methods: We investigated the association between either A2317G or HumDN1 polymorphism of deoxyribonuclease I gene and AMI in Han Chinese population. A2317G and HumDN1 polymorphisms in 278 AMI patients and 297 unrelated controls were detected by PCR and PCR-restriction fragment length polymorphism. Plasma lipids were measured in fasting state by biochemical methods.Results: A new HumDN1 genotype—HumDN1 4/6 was found in Han Chinese AMI patients. Genotype distributions and allele frequencies of A2317G and HumDN1 did not differ between AMI patients and control group (all P>0.05). In addition, none of estimated haplotypes significantly increased or decreased the risk of AMI. In analysis of covariance, plasma total cholesterol was observed to be associated with HumDN1 genotypes in AMI patients (P=0.02).Conclusions: Our data suggest HumDN1 genotypes are related to total cholesterol levels in Han Chinese AMI patients, but deoxyribonuclease I gene polymorphisms are not associated with susceptibility to AMI in Han Chinese.Association of deoxyribonuclease I genetic polymorphisms with unstable angina pectoris in Han ChineseBackground: Unstable angina pectoris (UAP) shared the same mechanism of pathogenesis with myocardial infarction. However, the relationship between deoxyribonuclease I gene polymorphisms and UAP has not been reported.Methods: A2317G and HumDN1 polymorphisms in 196 UAP patients and 297 unrelated controls were detected by PCR and PCR-restriction fragment length polymorphism. Plasma lipids were measured in fasting state by biochemical methods. Results: Genotype distributions and allele frequencies of A2317G and HumDN1 did not differ between UAP patients and control group (all P>0.05). None of estimated haplotypes significantly increased or decreased the risk of UAP. In analysis of covariance, plasma lipids were not associated with deoxyribonuclease I genotypes in UAP patients (all P>0.05).Conclusions: Deoxyribonuclease I gene polymorphisms are not associated with susceptibility to UAP in Han Chinese.Part 3 Association of deoxyribonuclease I and apolipoprotein E genetic polymorphisms with coronary artery disease in Han ChineseBackground: Apolipoproteinε4, as a genetic predictor for CAD, has direct effect on lipid metabolism. Deoxyribonuclease I, a new proposed susceptible gene for myocardial infarction, had been found to be associated with serum total cholesterol levels by us. As for the relationship between these two CAD susceptible genes had not been clarified.Methods: In the present study, apolipoprotein E gene polymorphisms in 474 CAD patients (including 196 UAP patients and 278 MI patients) and 297 unrelated controls were detected by amplification refractory mutation system (ARMS). At the same time, plasma lipids were measured in fasting state by biochemical methods.Results: ApoEε4 allele was significantly more prevalent in CAD patients than in controls (P<0.05). ApoE polymorphism was associated with significant differences in total cholesterol, LDL cholesterol and ApoB. After adjustment for age, sex, hypertension, diabetes and smoking, E2/X carriers had the lowest mean total cholesterol, LDL-C, ApoB concentration, and subjects with E4/X genotype had the highest levels (P<0.05). R×Cχ2 analysis showed no relationship between apolipoprotein E and deoxyribonuclease I gene polymorphisms (P>0.05).Conclusions: Apolipoprotein E gene polymorphisms affect serum TC, LDL-C and ApoB levels in CAD. While, deoxyribonuclease I gene polymorphisms are not associated with ApoE genotypes in Han Chinese.