Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

Michella Ghassibe-Sabbagh; Daniel E Platt; Sonia Youhanna; Antoine B Abchee; Krista Stewart; Danielle A Badro; Marc Haber; Angelique K Salloum; Bouchra Douaihy; Hamid el Bayeh; Raed Othman; Nabil Shasha; Samer Kibbani; Elie Chammas; Aline Milane; Rita Nemr; Yoichiro Kamatani; Jörg Hager; Jean-Baptiste Cazier; Dominique Gauguier; Pierre A Zalloua; FGENTCARD Consortium

doi:10.1016/j.atherosclerosis.2012.02.035

Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

Michella Ghassibe-Sabbagh, Daniel E Platt, Sonia Youhanna, Antoine B Abchee, Krista Stewart, Danielle A Badro, Marc Haber, Angelique K Salloum, Bouchra Douaihy, Hamid el Bayeh, Raed Othman, Nabil Shasha, Samer Kibbani, Elie Chammas, Aline Milane, Rita Nemr, Yoichiro Kamatani, Jörg Hager, Jean-Baptiste Cazier, Dominique GauguierPierre A Zalloua, FGENTCARD Consortium

Cancer and Genomic Sciences

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

21 Citations (Scopus)

Abstract

BACKGROUND: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.

AIMS: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.

METHODS: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.

RESULTS: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.

CONCLUSIONS: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.

Original language	English
Pages (from-to)	180-6
Number of pages	7
Journal	Atherosclerosis
Volume	222
Issue number	1
Early online date	28 Feb 2012
DOIs	https://doi.org/10.1016/j.atherosclerosis.2012.02.035
Publication status	Published - May 2012

Keywords

Adult
Aged
Constriction, Pathologic
Coronary Artery Disease
Diuretics
Female
Gene-Environment Interaction
Homocysteine
Humans
Hyperhomocysteinemia
Hypertension
Lebanon
Logistic Models
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Organic Anion Transporters
Polymorphism, Genetic
Risk Factors

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Ghassibe-Sabbagh, M., Platt, D. E., Youhanna, S., Abchee, A. B., Stewart, K., Badro, D. A., Haber, M., Salloum, A. K., Douaihy, B., el Bayeh, H., Othman, R., Shasha, N., Kibbani, S., Chammas, E., Milane, A., Nemr, R., Kamatani, Y., Hager, J., Cazier, J.-B., ... FGENTCARD Consortium (2012). Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis, 222(1), 180-6. https://doi.org/10.1016/j.atherosclerosis.2012.02.035

@article{3b039c2af5464279a12843d4a7f59c49,

title = "Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk",

abstract = "BACKGROUND: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.AIMS: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.METHODS: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.RESULTS: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.CONCLUSIONS: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.",

keywords = "Adult, Aged, Constriction, Pathologic, Coronary Artery Disease, Diuretics, Female, Gene-Environment Interaction, Homocysteine, Humans, Hyperhomocysteinemia, Hypertension, Lebanon, Logistic Models, Male, Methylenetetrahydrofolate Reductase (NADPH2), Middle Aged, Organic Anion Transporters, Polymorphism, Genetic, Risk Factors",

author = "Michella Ghassibe-Sabbagh and Platt, {Daniel E} and Sonia Youhanna and Abchee, {Antoine B} and Krista Stewart and Badro, {Danielle A} and Marc Haber and Salloum, {Angelique K} and Bouchra Douaihy and {el Bayeh}, Hamid and Raed Othman and Nabil Shasha and Samer Kibbani and Elie Chammas and Aline Milane and Rita Nemr and Yoichiro Kamatani and J{\"o}rg Hager and Jean-Baptiste Cazier and Dominique Gauguier and Zalloua, {Pierre A} and {FGENTCARD Consortium}",

year = "2012",

month = may,

doi = "10.1016/j.atherosclerosis.2012.02.035",

language = "English",

volume = "222",

pages = "180--6",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier",

number = "1",

}

Ghassibe-Sabbagh, M, Platt, DE, Youhanna, S, Abchee, AB, Stewart, K, Badro, DA, Haber, M, Salloum, AK, Douaihy, B, el Bayeh, H, Othman, R, Shasha, N, Kibbani, S, Chammas, E, Milane, A, Nemr, R, Kamatani, Y, Hager, J, Cazier, J-B, Gauguier, D, Zalloua, PA & FGENTCARD Consortium 2012, 'Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk', Atherosclerosis, vol. 222, no. 1, pp. 180-6. https://doi.org/10.1016/j.atherosclerosis.2012.02.035

TY - JOUR

T1 - Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

AU - Ghassibe-Sabbagh, Michella

AU - Platt, Daniel E

AU - Youhanna, Sonia

AU - Abchee, Antoine B

AU - Stewart, Krista

AU - Badro, Danielle A

AU - Haber, Marc

AU - Salloum, Angelique K

AU - Douaihy, Bouchra

AU - el Bayeh, Hamid

AU - Othman, Raed

AU - Shasha, Nabil

AU - Kibbani, Samer

AU - Chammas, Elie

AU - Milane, Aline

AU - Nemr, Rita

AU - Kamatani, Yoichiro

AU - Hager, Jörg

AU - Cazier, Jean-Baptiste

AU - Gauguier, Dominique

AU - Zalloua, Pierre A

AU - FGENTCARD Consortium

PY - 2012/5

Y1 - 2012/5

N2 - BACKGROUND: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.AIMS: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.METHODS: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.RESULTS: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.CONCLUSIONS: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.

AB - BACKGROUND: Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.AIMS: The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.METHODS: A total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.RESULTS: Traditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.CONCLUSIONS: Hyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics' intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.

KW - Adult

KW - Aged

KW - Constriction, Pathologic

KW - Coronary Artery Disease

KW - Diuretics

KW - Female

KW - Gene-Environment Interaction

KW - Homocysteine

KW - Humans

KW - Hyperhomocysteinemia

KW - Hypertension

KW - Lebanon

KW - Logistic Models

KW - Male

KW - Methylenetetrahydrofolate Reductase (NADPH2)

KW - Middle Aged

KW - Organic Anion Transporters

KW - Polymorphism, Genetic

KW - Risk Factors

U2 - 10.1016/j.atherosclerosis.2012.02.035

DO - 10.1016/j.atherosclerosis.2012.02.035

M3 - Article

C2 - 22425167

SN - 0021-9150

VL - 222

SP - 180

EP - 186

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

ER -

Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

Abstract

Keywords

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