Candidate Gene Association Analysis Of Dilated Cardiomyopathy In Chinese Han Population

BackgroundThe incidence of dilated cardiomyopathy（DCM）has increased recently,and a consider amount of effort has been undertaken to understand this condition further.DCM and cardiac manifestations of neonatal lupus（cardiac-NL）are both associated with inflammation and myocardial fibrosis,suggesting that there may be a connection between the two conditions.A recent genome-wide association study（GWAS）and large-scale research have identified NCR3,NOTCH4,CYP1A2,ITGA1,OPRM1,ST8SIA2,and LINC00704 as genetic risk factors associated with cardiac-NL.But whether these genes confer susceptibility to DCM in Chinese Han population remain to be studied.ObjectiveOur study aimed to investigate the relationship between NCR3,NOTCH4,CYP1A2,ITGA1,OPRM1,ST8SIA2,and LINC00704 and DCM in the Chinese Han population,also the relationship between these loci and clinical indices of DCM.MethodsThe present study was designed as a case–control study.273 DCM cases and548 controls of Chinese Han were collected and all subjects were unrelated and self-reported as Han Chinese ethnicity.Seven single nucleotide polymorphisms（SNPs）in the NCR3 region（rs2857595）,NOTCH4 region（rs3134942）,CYP1A2region（rs2472299）,ITGA1 region（rs2432143）,OPRM1 region（rs2272381）,ST8SIA2 region（rs1487982）,and LINC00704 region（rs1391511）were genotyped by using MALDI-TOF-MS.ResultsLogistic regression analysis showed that the allele T of rs3134942 in NOTCH4gene may increased DCM risk by 61%compared to the allele G(OR=1.61,95%CI:1.15–2.27,P_a=6.57×10^-3).Besides,for SNP rs2472299 of CYP1A2 gene,an association was shown in the dominant model(OR:0.72,95%CI:0.53–0.97,P_a=2.98×10^-2)and observed to correlate with smoking status（OR=0.60,95%CI:0.83–1.70,P_a=1.56×10-2）.No association was found between other SNPs and genetic models or the clinical index of DCM（P_a>0.05）.ConclusionThe present study was the first to demonstrate the relationship between NOTCH4 and CYP1A2 genes polymorphisms and DCM,and suggested that NOTCH4and CYP1A2 represent novel susceptibility genes for DCM in the Chinese Han population.