title: Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia.
abstract: OBJECTIVE
  Recent large association studies have revealed associations between genetic polymorphisms and myocardial infarction and coronary heart disease (CHD). We performed a replication study of 10 polymorphisms and CHD in a population with familial hypercholesterolemia (FH), individuals at extreme risk of CHD.
  
  
  RESULTS
  We genotyped 10 polymorphisms in 2145 FH patients and studied the association between these polymorphisms and CHD in Cox proportional hazards models. We confirmed the associations between four polymorphisms and CHD, the rs1151640 polymorphism in the olfactory receptor family 13 subfamily G member 1 (OR13G1) gene (HR 1.14, 95% CI 1.01-1.28, P = 0.03), the rs11881940 polymorphism in the heterogeneous nuclear ribonucleoprotein U-like 1 (HNRPUL1) gene (HR 1.27, 95% CI 1.07-1.51, P = 0.007), the rs3746731 polymorphism in the complement component 1 q subcomponent receptor 1 (CD93) gene (HR 1.26, 95% CI 1.06-1.49, P = 0.01), and the rs10757274 polymorphism near the cyclin-dependent kinase N2A and N2B (CDKN2A and CDKN2B) genes (HR 1.39, 95% CI 1.15-1.69, P < 0.001).
  
  
  CONCLUSIONS
  We confirmed previously found associations between four polymorphisms and CHD, but refuted associations for six other polymorphisms in our large FH population. These findings stress the importance of replication before genetic information can be implemented in the prediction of CHD.
authors.affiliation: Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jeroen B
authors.initials: JB
authors.lastname: van der Net
authors.forename: Daniëlla M
authors.initials: DM
authors.lastname: Oosterveer
authors.forename: Jorie
authors.initials: J
authors.lastname: Versmissen
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.forename: Mojgan
authors.initials: M
authors.lastname: Yazdanpanah
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D005838:Genotype; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000009:adverse effects / Q000235:genetics; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000009:adverse effects / Q000235:genetics; D008875:Middle Aged; D009687:Nuclear Proteins / Q000009:adverse effects / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011951:Receptors, Complement / Q000235:genetics; D018035:Receptors, Odorant / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000009:adverse effects / Q000235:genetics
chemical_list: C475078:HNRNPUL1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C514887:OR2AG1 protein, human; D011951:Receptors, Complement; D018035:Receptors, Odorant; D014157:Transcription Factors; C032402:complement 1q receptor; D000808:Angiotensinogen; D002784:Cholesterol