Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia

Karen S. Brown; Leo A.J. Kluijtmans; Ian S. Young; Jayne Woodside; John W.G. Yarnell; Dorothy McMaster; Liam Murray; Alun E. Evans; Colin A. Boreham; Helene McNulty; J. J. Strain; Laura E. Mitchell; Alexander S. Whitehead

doi:10.1161/01.ATV.0000071348.70527.F4

Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia

Karen S. Brown, Leo A.J. Kluijtmans, Ian S. Young, Jayne Woodside, John W.G. Yarnell, Dorothy McMaster, Liam Murray, Alun E. Evans, Colin A. Boreham, Helene McNulty, J. J. Strain, Laura E. Mitchell, Alexander S. Whitehead

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

Objective - Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism. Methods and Results - The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P=0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population. Conclusions - These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.

Original language	English
Pages (from-to)	1014-1020
Number of pages	7
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	23
Issue number	6
DOIs	https://doi.org/10.1161/01.ATV.0000071348.70527.F4
Publication status	Published (in print/issue) - 1 Jun 2003

Keywords

5,10-methylenetetrahydrofolate reductase
Hyperhomocystenemia
Nitric oxide
Nitric oxide synthase
Smoking

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/01.ATV.0000071348.70527.F4

Cite this

Brown, K. S., Kluijtmans, L. A. J., Young, I. S., Woodside, J., Yarnell, J. W. G., McMaster, D., Murray, L., Evans, A. E., Boreham, C. A., McNulty, H., Strain, J. J., Mitchell, L. E., & Whitehead, A. S. (2003). Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(6), 1014-1020. https://doi.org/10.1161/01.ATV.0000071348.70527.F4

@article{f4c2123fdb5c446185faa8ebda08d7ae,

title = "Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia",

abstract = "Objective - Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism. Methods and Results - The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P=0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population. Conclusions - These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.",

keywords = "5,10-methylenetetrahydrofolate reductase, Hyperhomocystenemia, Nitric oxide, Nitric oxide synthase, Smoking",

author = "Brown, {Karen S.} and Kluijtmans, {Leo A.J.} and Young, {Ian S.} and Jayne Woodside and Yarnell, {John W.G.} and Dorothy McMaster and Liam Murray and Evans, {Alun E.} and Boreham, {Colin A.} and Helene McNulty and Strain, {J. J.} and Mitchell, {Laura E.} and Whitehead, {Alexander S.}",

year = "2003",

month = jun,

day = "1",

doi = "10.1161/01.ATV.0000071348.70527.F4",

language = "English",

volume = "23",

pages = "1014--1020",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "American Heart Association",

number = "6",

}

Brown, KS, Kluijtmans, LAJ, Young, IS, Woodside, J, Yarnell, JWG, McMaster, D, Murray, L, Evans, AE, Boreham, CA, McNulty, H , Strain, JJ, Mitchell, LE & Whitehead, AS 2003, 'Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 6, pp. 1014-1020. https://doi.org/10.1161/01.ATV.0000071348.70527.F4

TY - JOUR

T1 - Genetic evidence that nitric oxide modulates homocysteine

T2 - The NOS3 894TT genotype is a risk factor for hyperhomocystenemia

AU - Brown, Karen S.

AU - Kluijtmans, Leo A.J.

AU - Young, Ian S.

AU - Woodside, Jayne

AU - Yarnell, John W.G.

AU - McMaster, Dorothy

AU - Murray, Liam

AU - Evans, Alun E.

AU - Boreham, Colin A.

AU - McNulty, Helene

AU - Strain, J. J.

AU - Mitchell, Laura E.

AU - Whitehead, Alexander S.

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Objective - Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism. Methods and Results - The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P=0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population. Conclusions - These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.

AB - Objective - Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism. Methods and Results - The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P=0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population. Conclusions - These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.

KW - 5,10-methylenetetrahydrofolate reductase

KW - Hyperhomocystenemia

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Smoking

UR - http://www.scopus.com/inward/record.url?scp=12444264831&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.0000071348.70527.F4

DO - 10.1161/01.ATV.0000071348.70527.F4

M3 - Article

C2 - 12689917

AN - SCOPUS:12444264831

SN - 1079-5642

VL - 23

SP - 1014

EP - 1020

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 6

ER -

Genetic evidence that nitric oxide modulates homocysteine: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this