Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

van Meurs, J.B.; Pare, G.; Schwartz, S.M.; Hazra, A.; Tanaka, T.; Vermeulen, S.H.; Cotlarciuc, I.; Yuan, X.; MÃ¤larstig A.,; Bandinelli, S.; Bis, J.C.; Blom, H.; Brown, M.J.; Chen, C.; Chen, Y.D.; Clarke, R.J.; Dehghan, A.; Erdmann, J.; Ferrucci, L.; Hamsten, A.; Hofman, A.; Hunter, D.J.; Goel, A.; Johnson, A.D.; Kathiresan, S.; Kampman, E.; Kiel, D.P.; Kiemeney, L.A.; Chambers, J.C.; Kraft, P.; Lindemans, J.; McKnight, B.; Nelson, C.P.; O'Donnell, C.J.; Psaty, B.M.; Ridker, P.M.; Rivadeneira, F.; Rose, L.M.; Seedorf, U.; Siscovick, D.S.; Schunkert, H.; Selhub, J.; Ueland, P.M.; Vollenweider, P.; Waeber, G.; Waterworth, D.M.; Watkins, H.; Witteman, J.C.; den Heijer, M.; Jacques, P.; Uitterlinden, A.G.; Kooner, J.S.; Rader, D.J.; Reilly, M.P.; Mooser, V.; Chasman, D.I.; Samani, N.J.; Ahmadi, K.R.

doi:10.3945/ajcn.112.044545

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

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Serval ID

serval:BIB_E64FA38F2AEB

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

Journal

American Journal of Clinical Nutrition

Author(s)

van Meurs J.B., Pare G., Schwartz S.M., Hazra A., Tanaka T., Vermeulen S.H., Cotlarciuc I., Yuan X., MÃ¤larstig A. , Bandinelli S., Bis J.C., Blom H., Brown M.J., Chen C., Chen Y.D., Clarke R.J., Dehghan A., Erdmann J., Ferrucci L., Hamsten A., Hofman A., Hunter D.J., Goel A., Johnson A.D., Kathiresan S., Kampman E., Kiel D.P., Kiemeney L.A., Chambers J.C., Kraft P., Lindemans J., McKnight B., Nelson C.P., O'Donnell C.J., Psaty B.M., Ridker P.M., Rivadeneira F., Rose L.M., Seedorf U., Siscovick D.S., Schunkert H., Selhub J., Ueland P.M., Vollenweider P., Waeber G., Waterworth D.M., Watkins H., Witteman J.C., den Heijer M., Jacques P., Uitterlinden A.G., Kooner J.S., Rader D.J., Reilly M.P., Mooser V., Chasman D.I., Samani N.J., Ahmadi K.R.

ISSN

1938-3207 (Electronic)

ISSN-L

0002-9165

Publication state

Published

Issued date

2013

Peer-reviewed

Oui

Volume

Number

Pages

668-676

Language

english

Notes

Publication types: Journal Article Publication Status: ppublish

Abstract

BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD.
OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD.
DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls.
RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 Ã- 10(-9)), SLC17A3 (1.0 Ã- 10(-8)), GTPB10 (1.7 Ã- 10(-8)), CUBN (7.5 Ã- 10(-10)), HNF1A (1.2 Ã- 10(-12)), and FUT2 (6.6 Ã- 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-Î¼mol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 Ã- 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49).
CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

OAI-PMH

oai:serval.unil.ch:BIB_E64FA38F2AEB

DOI

10.3945/ajcn.112.044545

Pubmed

23824729

Web of science

000323532700007

Open Access

Yes

Create date

20/09/2013 18:09