Common Polymorphism In 3 ' End Intergenic Regions Of APOA1 And APOC3 Associated With Plasma Triglycerides Levels And Coronary Heart Disease

AimsMany studies have reported the associations between dyslipidemia and APOA1/C3/A4/A5 gene cluster polymorphisms,which increasing the risk of coronary heart disease.In this gene cluster,there is a 3'end intergenic DNA region co-owned by APOA1 and APOC3 gene,which is resulting from opposite transcribed direction and 2.7 kilo bases in size.The aim of this study was to investigate the effects of common SNPs in this genetic region on the expression of the gene cluster and the level of blood lipid,and then explore the relevance in CAD and potential underlying mechanisms.Methods and resultsWe resequenced the intergenic DNA region in 164 healthy controls and then genotyped 5 tag SNPs among 1233 CAD patients and 1233 sex,age and geography matched controls in two case-control groups.The results showed that P_recessiveecessive and P_additivedditive values of three SNPs?rs7123454,rs10750098 and rs12721028?,were statistical significant?P<0.05?,while P_additivedditive of rs12721030 was marginally significant in initial study?population set 1?.These results were successfully replicated under the recessive genetic model in the second independent cohort?population set 2?.Combined analysis from data set 1 and set 2 showed an even stronger association between CHD with rs7123454(OR:0.71,95%CI:0.59–0.85;P_recessive<0.001),rs12721030(OR:0.70,95%CI:0.53-0.92,P_recessive=0.01),rs10750098(OR:0.73,95%CI:0.62-0.87,P_recessive<0.01)as well as rs12721028(OR:0.44,95%CI:0.32-0.60;P_recessive<0.01)with adjustment for clinical covariates and different population sets.No significant association was found between the rs525028 and CHD risk in both two groups.ConclusionsCommon SNPs in intergenic DNA region of APOA1 and APOC3 may play an important role in the regulation of APOA1 and APOC3 genes and affect plasma lipids levels.SNP rs7123454 A,rs12721030 T,rs10750098 T and rs12721028 G contribute to the protection of CAD.ObjectivesIt had been reported that mitochondria DNA?mt DNA?was related to reactive oxidative stress?ROS?.And the generation of mitochondrial ROS played an important role in the pathogenesis of stroke.Hence,we proposed the hypothesis that mt DNA copy number variants might confer the risk to ischemic stroke.MethodsWe used quantitative polymerase chain reaction in triplicate to detect the content of mt DNA?Mitochondrial DNA?in 721 ischemic stroke patients and 721 age-sex well matched control subjects.ResultsThe mean relative mt DNA copy number was higher in ischemic stroke patients compared to healthy subjects?2.71±0.79 vs.2.49±0.69,p<0.001?.With adjustment of traditional risk factors,patients with higher relative mt DNA copy number exposed higher risk of ischemic stroke.As compared with the first quartile?the smallest?,the odd ratios?OR?and 95%confidence intervals?CI?for ischemic stroke risk were as follows: the second quartile OR=1.87,95%CI: 1.32-2.66,P<0.001;the third quartile OR=2.50,95%CI: 1.78-3.51,P<0.001;the forth quartile OR=2.29,95%CI: 1.62-3.24,P<0.001,respectively.Conclusions:Higher mt DNA copy number was an independent risk factor for ischemic stroke.