Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Genetic variants in SUSD2 are associated with the risk of ischemic heart disease

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bruikman, CS, Dalila, N, van Capelleveen, JC, Kroon, J, Peter, J, Havik, SR, Willems, M, Huisman, LC, de Boer, OJ, Hovingh, GK, Tybjaerg-Hansen, A & Dallinga-Thie, GM 2020, 'Genetic variants in SUSD2 are associated with the risk of ischemic heart disease', Journal of Clinical Lipidology, vol. 14, no. 4, pp. 470-481. https://doi.org/10.1016/j.jacl.2020.05.100

APA

Bruikman, C. S., Dalila, N., van Capelleveen, J. C., Kroon, J., Peter, J., Havik, S. R., Willems, M., Huisman, L. C., de Boer, O. J., Hovingh, G. K., Tybjaerg-Hansen, A., & Dallinga-Thie, G. M. (2020). Genetic variants in SUSD2 are associated with the risk of ischemic heart disease. Journal of Clinical Lipidology, 14(4), 470-481. https://doi.org/10.1016/j.jacl.2020.05.100

CBE

Bruikman CS, Dalila N, van Capelleveen JC, Kroon J, Peter J, Havik SR, Willems M, Huisman LC, de Boer OJ, Hovingh GK, Tybjaerg-Hansen A, Dallinga-Thie GM. 2020. Genetic variants in SUSD2 are associated with the risk of ischemic heart disease. Journal of Clinical Lipidology. 14(4):470-481. https://doi.org/10.1016/j.jacl.2020.05.100

MLA

Vancouver

Author

Bruikman, Caroline S ; Dalila, Nawar ; van Capelleveen, Julian C ; Kroon, Jeffrey ; Peter, Jorge ; Havik, Stefan R ; Willems, Martine ; Huisman, Laurens C ; de Boer, Onno J ; Hovingh, G Kees ; Tybjaerg-Hansen, Anne ; Dallinga-Thie, Geesje M. / Genetic variants in SUSD2 are associated with the risk of ischemic heart disease. In: Journal of Clinical Lipidology. 2020 ; Vol. 14, No. 4. pp. 470-481.

Bibtex

@article{1c6c73e6e5b84220bbb3ac5e1a367677,
title = "Genetic variants in SUSD2 are associated with the risk of ischemic heart disease",
abstract = "BACKGROUND: Genetic factors partly determine the risk for premature myocardial infarction (MI).OBJECTIVES: We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study.METHODS: Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis. A common variant, rs8141797 A>G (p.Asn466Ser), in sushi domain-containing protein 2 (SUSD2) was studied in the prospective Copenhagen General Population Studies (N = 105,408) for association with IHD.RESULTS: A novel heterozygous nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) was associated with the disease phenotype in the pedigree. SUSD2 protein was expressed in aortic specimens in the subendothelial cell layer and around the vasa vasorum. Furthermore, the minor G-allele of rs8141797 was associated with per allele higher levels of SUSD2 mRNA expression in the heart and vasculature. In the Copenhagen General Population Study, hazard ratios for IHD were 0.92 (95% CI: 0.87-0.97) in AG heterozygotes and 0.86 (0.62-1.19) in GG homozygotes vs noncarrriers (P-trend = .002). Finally, in meta-analysis including 73,983 IHD cases and 215,730 controls, the odds ratio for IHD per G-allele vs A-allele was 0.93 (0.90-0.96) (P = 4.6 × 10-7).CONCLUSIONS: The identification of a truncating mutation in SUSD2, which was associated with premature MI and subclinical atherosclerosis, combined with the finding that a common missense variant in SUSD2 was strongly associated with a lower risk of IHD, suggest that SUSD2 may alter the risk of atherosclerosis.",
keywords = "Epidemiology, Genetics, Human, Myocardial infarction, Premature atherosclerosis, SUSD2",
author = "Bruikman, {Caroline S} and Nawar Dalila and {van Capelleveen}, {Julian C} and Jeffrey Kroon and Jorge Peter and Havik, {Stefan R} and Martine Willems and Huisman, {Laurens C} and {de Boer}, {Onno J} and Hovingh, {G Kees} and Anne Tybjaerg-Hansen and Dallinga-Thie, {Geesje M}",
note = "Copyright {\textcopyright} 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = jul,
day = "6",
doi = "10.1016/j.jacl.2020.05.100",
language = "English",
volume = "14",
pages = "470--481",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
publisher = "Elsevier Inc",
number = "4",

}

RIS

TY - JOUR

T1 - Genetic variants in SUSD2 are associated with the risk of ischemic heart disease

AU - Bruikman, Caroline S

AU - Dalila, Nawar

AU - van Capelleveen, Julian C

AU - Kroon, Jeffrey

AU - Peter, Jorge

AU - Havik, Stefan R

AU - Willems, Martine

AU - Huisman, Laurens C

AU - de Boer, Onno J

AU - Hovingh, G Kees

AU - Tybjaerg-Hansen, Anne

AU - Dallinga-Thie, Geesje M

N1 - Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.

PY - 2020/7/6

Y1 - 2020/7/6

N2 - BACKGROUND: Genetic factors partly determine the risk for premature myocardial infarction (MI).OBJECTIVES: We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study.METHODS: Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis. A common variant, rs8141797 A>G (p.Asn466Ser), in sushi domain-containing protein 2 (SUSD2) was studied in the prospective Copenhagen General Population Studies (N = 105,408) for association with IHD.RESULTS: A novel heterozygous nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) was associated with the disease phenotype in the pedigree. SUSD2 protein was expressed in aortic specimens in the subendothelial cell layer and around the vasa vasorum. Furthermore, the minor G-allele of rs8141797 was associated with per allele higher levels of SUSD2 mRNA expression in the heart and vasculature. In the Copenhagen General Population Study, hazard ratios for IHD were 0.92 (95% CI: 0.87-0.97) in AG heterozygotes and 0.86 (0.62-1.19) in GG homozygotes vs noncarrriers (P-trend = .002). Finally, in meta-analysis including 73,983 IHD cases and 215,730 controls, the odds ratio for IHD per G-allele vs A-allele was 0.93 (0.90-0.96) (P = 4.6 × 10-7).CONCLUSIONS: The identification of a truncating mutation in SUSD2, which was associated with premature MI and subclinical atherosclerosis, combined with the finding that a common missense variant in SUSD2 was strongly associated with a lower risk of IHD, suggest that SUSD2 may alter the risk of atherosclerosis.

AB - BACKGROUND: Genetic factors partly determine the risk for premature myocardial infarction (MI).OBJECTIVES: We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study.METHODS: Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis. A common variant, rs8141797 A>G (p.Asn466Ser), in sushi domain-containing protein 2 (SUSD2) was studied in the prospective Copenhagen General Population Studies (N = 105,408) for association with IHD.RESULTS: A novel heterozygous nonsense mutation in SUSD2 (c.G583T; p.Glu195Ter) was associated with the disease phenotype in the pedigree. SUSD2 protein was expressed in aortic specimens in the subendothelial cell layer and around the vasa vasorum. Furthermore, the minor G-allele of rs8141797 was associated with per allele higher levels of SUSD2 mRNA expression in the heart and vasculature. In the Copenhagen General Population Study, hazard ratios for IHD were 0.92 (95% CI: 0.87-0.97) in AG heterozygotes and 0.86 (0.62-1.19) in GG homozygotes vs noncarrriers (P-trend = .002). Finally, in meta-analysis including 73,983 IHD cases and 215,730 controls, the odds ratio for IHD per G-allele vs A-allele was 0.93 (0.90-0.96) (P = 4.6 × 10-7).CONCLUSIONS: The identification of a truncating mutation in SUSD2, which was associated with premature MI and subclinical atherosclerosis, combined with the finding that a common missense variant in SUSD2 was strongly associated with a lower risk of IHD, suggest that SUSD2 may alter the risk of atherosclerosis.

KW - Epidemiology

KW - Genetics

KW - Human

KW - Myocardial infarction

KW - Premature atherosclerosis

KW - SUSD2

UR - http://www.scopus.com/inward/record.url?scp=85087343456&partnerID=8YFLogxK

U2 - 10.1016/j.jacl.2020.05.100

DO - 10.1016/j.jacl.2020.05.100

M3 - Journal article

C2 - 32620384

VL - 14

SP - 470

EP - 481

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

SN - 1933-2874

IS - 4

ER -

ID: 60897562