Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia

Jeroen B. Van Der Net, Daniëlla M. Oosterveer, Jorie Versmissen, Joep C. Defesche, Mojgan Yazdanpanah, Bradley E. Aouizerat, Ewout W. Steyerberg, Mary J. Malloy, Clive R. Pullinger, John J P Kastelein, John P. Kane, Eric J G Sijbrands

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2195-2201
Number of pages7
JournalEuropean Heart Journal
Volume29
Issue number18
DOIs
StatePublished - Sep 2008

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Hyperlipoproteinemia Type II
Genetic Polymorphisms
Coronary Disease
Population
Heterogeneous-Nuclear Ribonucleoprotein U
Odorant Receptors
Complement C1
Genes
p16 Genes
Cyclin-Dependent Kinases
Proportional Hazards Models
Myocardial Infarction

Keywords

  • Coronary heart disease
  • Familial hypercholesterolemia
  • Genetics
  • Polymorphism
  • Replication

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia. / Van Der Net, Jeroen B.; Oosterveer, Daniëlla M.; Versmissen, Jorie; Defesche, Joep C.; Yazdanpanah, Mojgan; Aouizerat, Bradley E.; Steyerberg, Ewout W.; Malloy, Mary J.; Pullinger, Clive R.; Kastelein, John J P; Kane, John P.; Sijbrands, Eric J G.

In: European Heart Journal, Vol. 29, No. 18, 09.2008, p. 2195-2201.

Research output: Contribution to journalArticle

Van Der Net, JB, Oosterveer, DM, Versmissen, J, Defesche, JC, Yazdanpanah, M, Aouizerat, BE, Steyerberg, EW, Malloy, MJ, Pullinger, CR, Kastelein, JJP, Kane, JP & Sijbrands, EJG 2008, 'Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia', European Heart Journal, vol. 29, no. 18, pp. 2195-2201. https://doi.org/10.1093/eurheartj/ehn303
Van Der Net, Jeroen B. ; Oosterveer, Daniëlla M. ; Versmissen, Jorie ; Defesche, Joep C. ; Yazdanpanah, Mojgan ; Aouizerat, Bradley E. ; Steyerberg, Ewout W. ; Malloy, Mary J. ; Pullinger, Clive R. ; Kastelein, John J P ; Kane, John P. ; Sijbrands, Eric J G. / Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia. In: European Heart Journal. 2008 ; Vol. 29, No. 18. pp. 2195-2201.
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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

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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.

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