TY - JOUR
T1 - Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia
AU - Van Der Net, Jeroen B.
AU - Oosterveer, Daniëlla M.
AU - Versmissen, Jorie
AU - Defesche, Joep C.
AU - Yazdanpanah, Mojgan
AU - Aouizerat, Bradley E.
AU - Steyerberg, Ewout W.
AU - Malloy, Mary J.
AU - Pullinger, Clive R.
AU - Kastelein, John J P
AU - Kane, John P.
AU - Sijbrands, Eric J G
N1 - Funding Information:
This work was supported by grants from the Dutch Heart Foundation (2007R017 and 2006B190), the Trust Foundation of the Erasmus University Rotterdam (J.B.N.), the American Heart Association (C.R.P.; 0655195Y), the Hellman Family Award (C.R.P.), the Leducq Foundation (C.R.P., M.J.M., J.P.K.), and NCRR (B.E.A.; KL2RR024130), a component of NIH.
PY - 2008/9
Y1 - 2008/9
N2 - Aims: 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. Methods and 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). Conclusion: 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.
AB - Aims: 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. Methods and 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). Conclusion: 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.
KW - Coronary heart disease
KW - Familial hypercholesterolemia
KW - Genetics
KW - Polymorphism
KW - Replication
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U2 - 10.1093/eurheartj/ehn303
DO - 10.1093/eurheartj/ehn303
M3 - Article
C2 - 18599554
AN - SCOPUS:52449108620
SN - 0195-668X
VL - 29
SP - 2195
EP - 2201
JO - European Heart Journal
JF - European Heart Journal
IS - 18
ER -