Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia.
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.
van der Net
Jeroen B
JB
Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
Oosterveer
Daniëlla M
DM
Versmissen
Jorie
J
Defesche
Joep C
JC
Yazdanpanah
Mojgan
M
Aouizerat
Bradley E
BE
Steyerberg
Ewout W
EW
Malloy
Mary J
MJ
Pullinger
Clive R
CR
Kastelein
John J P
JJ
Kane
John P
JP
Sijbrands
Eric J G
EJ
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
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