| Objective: In present study, we aim to explore the association between24SNPs and CHDrisk in Han Chinese, and to summarize the roles in CHD using meta-analysis of existing studieswith various ethnic groups.Methods:1.For the meta-analyses, a systematic search of PubMed, Web of Science, EMbaseand China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Data base wasperformed update to Sep2012. The meta-analyses were performed using the softwares Revman5.0and Stata11.0. We recruited angiography-proven CHD patients and angiography-normal controlsoriginated from Ningbo in the Eastern China. MassARRAY and Tm-shift PCR were performed totest the association between the significant SNPs and CHD.Results:1. Meta-analyses were performed to investigate the associations between threegenetic variants CDKN2BAS (rs4977574), CXCL12(rs1746048), SH2B3(rs3184504) and CHD.The pooled ORs suggest that rs1746048-C is a risk factor of CHD (P <0.0001, OR=1.11);rs4977574-G has a26%increased risk of CHD (P <0.0001, OR=1.26). rs3184504shows asignificant association with CHD in Europeans and Asians (P <0.0001, OR=1.13).2. In the case-control study, we find that IKZF2(rs12619285) and PDGFD (rs974819) are associated with CHDin the additive model (rs12619285: OR=1.25, P=0.03; rs974819: OR=1.45, P=0.04). CXCL12(rs1746048) and NOS1AP (rs10918859) show significant associations with CHD in additive anddominant models (rs1746048: additive: OR=1.28, P=0.02; dominant: OR=1.36, P=0.03;rs10918859: additive: OR=1.44, P=0.047; dominant: OR=2.02, P=0.005).3. In the gendersubgroup analysis, we find that IKZF2(rs12619285) and PDGFD (rs974819) are associated withCHD in the female additive model (rs12619285: OR=1.39, P=0.05; rs974819: OR=1.83, P=0.04). CXCL12(rs1746048) shows a weak association with CHD in male under the recessivemodel (OR=1.72, P=0.05). Strong connection has been found between NOS1AP (rs10918859)and CHD in male under the additive and dominant model (additive: OR=1.66, P=0.03; dominant:OR=2.46, P=0.0005). CDKN2BAS (rs4977574) relates to CHD in female under the additive andrecessive model (additive: OR=1.54, P=0.008; recessive: OR=2.29, P=0.002).4. The agesubgroup analysis proves that IKZF2(rs12619285) and CXCL12(rs1746048) have increased CHDrisk for the subjects aged65years or older (rs12619285: Genotype P=0.04, Allele P=0.03, OR=1.54; rs1746048: Genotype P=0.01, Allele P=0.003, OR=1.90). CDKN2BAS (rs4977574) is shown to increase70%risk of CHD in female aged less than65(Genotype P=0.01, Allele P=0.01, OR=1.70). No relationship is found in NOS1AP (rs10918859) and CHD in different agegroups (P>0.05).Conclusions:1. The meta-analyses indicate significant associations between CDKN2BAS (rs4977574),CXCL12(rs1746048), SH2B3(rs3184504) and CHD risk in different ethnic populations.2. Case-control study data show that there are no associations between CHD and the17polymorphisms: CELSR2(rs646776), IL1RL1(rs1420101), IL5(rs4144832), WDR12(rs6725887), MRAS (rs2306374), PHACTR1(rs12526453), PIK3CG (rs342293), BCAP29(rs10953541), LIPA (rs1412444), SH2B3(rs3184504), BRAP (rs3782886), ADAMTS7(rs4380028), LDLR (rs2228671), CASQ2(rs17500488), CASQ2(rs3010396), CASQ2(rs7366407) and NOS1AP (rs12084280). In the study, we conclude that CDKN2BAS(rs4977574), IKZF2(rs12619285), CXCL12(rs1746048), NOS1AP (rs10918859) andPDGFD (rs974819) are the susceptible locs of CHD in Han Chinese.3. IKZF2(rs12619285), PDGFD (rs974819) and CDKN2BAS (rs4977574) contact withCHD in the female Han Chinese. CXCL12(rs1746048) and NOS1AP (rs10918859) arelinked to CHD risk in the male.4. IKZF2(rs12619285) and CXCL12(rs1746048) have54%and91%increased risk of CHDfor the subjects aged65years or older. CDKN2BAS (rs4977574) is shown to increaseCHD risk in female younger than65. |
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