title: The associations between proprotein convertase subtilisin/kexin type 9 E670G polymorphism and the risk of coronary artery disease and serum lipid levels: a meta-analysis.
abstract: BACKGROUND
  Studies had investigated the associations between proprotein convertase subtilisin/kexin type 9 (PCSK9) E670G polymorphism and coronary artery disease (CAD) and lipid levels, but the results were controversial. Thus, we performed this meta-analysis to investigate the association between PCSK9 E670G polymorphism and lipid levels and the susceptibility to CAD.
  
  
  METHODS
  All relevant articles according to the inclusion criteria were retrieved and included in the present meta-analysis. Odds ratios (ORs) with 95 % confidence interval (CI) were used to analyze the strength of the association between PCSK9 E670G polymorphism and the susceptibility to CAD. At the same time, the pooled standardized mean difference (SMD) with 95 % CI was used for the meta-analysis of PCSK9 E670G polymorphism and lipid levels. The publication bias was examined by using Begg's funnel plots and Egger's test.
  
  
  RESULTS
  A total of seventeen studies met the inclusion criteria. For CAD association, the pooled effects indicated that the G allele carriers had higher risk of CAD than non-carriers in dominant genetic model (OR:1.601, 95 % CI: 1.314-1.951, P < 0.001), as well as in allelic genetic model (OR: 1.546, 95 % CI: 1.301-1.838, P < 0.001). When the subgroup analysis stratified by ethnicity and HWE was performed, the positive result existed in most of the subgroups. For lipid levels association, the pooled effects indicated that the G allele carriers had higher TC and LDL-C levels than the non-carriers (for TC, SMD: 0.126, 95 % CI: 0.023-0.229, P = 0.016; for LDL-C, SMD: 0.170, 95 % CI: 0.053-0.287, P = 0.004, respectively). There was no difference in the levels of TG and HDL-C between the G carriers and the non-carriers in the whole population (SMD: 0.031, 95 % CI: -0.048-0.110, P = 0.440; SMD: -0.123, 95 % CI: -0.251-0.006, P = 0.061, respectively). When the studies were stratified by ethnicity and type of study, the G carriers had higher TC levels than the non-carriers (SMD: 0.126, 95 % CI: 0.014-0.238, P = 0.027) in the non-Asian subgroup. The similar results existed in cohort subgroup. The association between PCSK9 E670G polymorphism and LDL-C levels was significant in all subgroups. Meanwhile, the G carriers had higher TG levels than the non-carriers (SMD: 0.113, 95 % CI: 0.012-0.214, P = 0.028) in the case-control subgroup. AG + GG genotypes had lower HDL-C levels than AA genotype in Asian subgroup (SMD: -0.224, 95 % CI: -0.423- -0.025, P = 0.027) and in case-control subgroup (SMD: -0.257, 95 % CI: -0.467--0.048, P = 0.016).
  
  
  CONCLUSIONS
  The present meta-analysis concluded that PCSK9 E670G polymorphism was associated with CAD risk and lipid levels.
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China. cgj982@126.com.
authors.forename: Gaojun
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Ganwei
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cardiology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood / Q000235:genetics*; D044469:Racial Groups; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases