The TagSNPs In GATA2Gene Associate With Coronary Artery Disease In The Chinese Han Population

Coronary artery disease (CAD) is caused by accumulation of lipids and otherinflammatory molecules in the coronary arteries, which may eventually lead to formationof plaques (atherosclerosis) and blockage or stenosis of blood flow, result in ischemia andmyocardial infarction (MI). CAD is a complex disease which causes significant morbidityand mortality worldwide. In China CAD causes more than80million deaths each year in.It is a multi-gene complex genetic disease caused by genetic and environmental factors,and their interactions.The first GWAS in the Chinese population identified one SNP in a putative genec6orf105(rs6903956) that was significantly associated with risk of CAD and MI.Real-time reverse transcription PCR analysis (RT-PCR) found that the expression level ofc6orf105mRNA was significantly decreased in the AG or AA genotype. Further studies inour Laboratory found that the expression level of c6orf105was regulated bytranscriptional factor GATA2at the transcriptional level. Based on these data, Ihypothesized that SNPs in GATA2we associated with risk of CAD. By analyzing allcommon SNPs in GATA2, two tagSNPs were identified, including rs2713604andrs2335052. Then, a case-control association study design was used to determine whetherSNPs rs2713604and rs2335052we associated with CAD.For rs2713604,1120CAD patients and1116controls without CAD (all of Han ethnicorigin) were genotyped and statistical analysis with PLINK and SPSS revealed thatrs2713604was not associated with CAD.For rs2335052,1281CAD patients and1316controls were genotyped. Allelicassociation analysis with PLINK showed that rs2335052was not associated with CAD(P=0.369). Genotypic association analysis identified a significant association betweenSNP rs2335052and CAD in a recessive inheritance model (P=0.013), but the associationbecame non-significant after adjusting for CAD risk factors (P=0.756). Under a dominantinheritance model, the association between SNP rs2335052and CAD was significantbefore and after adjustment (observed P=1.01x10-6，adjusted P=0.014).The data in this thesis suggest that SNP rs2335052in the GATA2gene may confer asignificant risk of CAD in an antosomal dominant model in the Chinese Han population.These results may be valuable for future understanding of the pathogeuesis.