Additive Effect of Polymorphisms in the IL-6, LTA, and TNF-α Genes and Plasma Fatty Acid Level Modulate Risk for the Metabolic Syndrome and Its Components (original) (raw)
Journal Article
1Nutrigenomics Research Group (C.M.P., J.F.F., H.M.R.), University College Dublin School of Public Health and Population Science, University College Dublin Conway Institute, University College Dublin, Dublin 4, Ireland
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2Institut National de la Santé et de la Recherche Médicale 476 Lipid Nutrients and Prevention of Metabolic Diseases (L.G., H.P., R.P., D.L.), Institut National de la Recherche Agronomique, 1260, Université de la Méditerranée, Faculté de Médecine, 13385 Marseille Cedex 05, France
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3Institut National de la Santé et de la Recherche Médicale Unité 557 (S.B., S.H.), Institut National de la Recherche Agronomique-Conservatoire National des Arts et Métiers, Université Paris 13, F-93017 Bobigny, France
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1Nutrigenomics Research Group (C.M.P., J.F.F., H.M.R.), University College Dublin School of Public Health and Population Science, University College Dublin Conway Institute, University College Dublin, Dublin 4, Ireland
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4Hitachi Dublin Laboratory (M.R.F., E.D.K., J.M.), Dublin 2, Ireland
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4Hitachi Dublin Laboratory (M.R.F., E.D.K., J.M.), Dublin 2, Ireland
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4Hitachi Dublin Laboratory (M.R.F., E.D.K., J.M.), Dublin 2, Ireland
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5Boston University School of Public Health (G.M.P., L.A.C.), Boston, Massachusetts 02118
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5Boston University School of Public Health (G.M.P., L.A.C.), Boston, Massachusetts 02118
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6Nutrition and Genomics Laboratory (J.S., J.M.O.), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111
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Accepted:
03 December 2009
Cite
Catherine M. Phillips, Louisa Goumidi, Sandrine Bertrais, Jane F. Ferguson, Martyn R. Field, Enda D. Kelly, John Mehegan, Gina M. Peloso, L. Adrienne Cupples, Jian Shen, Jose M. Ordovas, Ross McManus, Serge Hercberg, Henri Portugal, Denis Lairon, Richard Planells, Helen M. Roche, Additive Effect of Polymorphisms in the IL-6, LTA, and _TNF_-α Genes and Plasma Fatty Acid Level Modulate Risk for the Metabolic Syndrome and Its Components, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 3, 1 March 2010, Pages 1386–1394, https://doi.org/10.1210/jc.2009-1081
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Abstract
Context: Cytokine polymorphisms and dietary fat composition may influence the risk of the metabolic syndrome (MetS).
Objective: The objective of the study was to determine the relationship between lymphotoxin-α (LTA), _TNF_-α, and IL-6 gene polymorphisms with MetS risk and investigate whether plasma fatty acid composition, a biomarker of dietary fat intake, modulated these associations.
Design: Polymorphisms (LTA rs915654, _TNF_-α rs1800629, IL-6 rs1800797), biochemical measurements, and plasma fatty acids were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).
Results:LTA rs915654 minor A allele carriers and _TNF_-α rs1800629 major G allele homozygotes had increased MetS risk [odds ratio (OR) 1.37 (confidence interval [CI] 1.12–1.66), P = 0.002 and OR 1.35 (CI 1.08–1.70), P = 0.009] compared with their TT homozygotes and A allele carriers. Possession of the IL-6 rs1800797 GG genotype by the LTA and TNF-α risk genotype carriers further increased risk of the MetS [OR 2.10 (CI 1.19–3.71) P = 0.009], fasting hyperglycemia [OR 2.65 (CI 1.12–6.28), P = 0.027], high systolic blood pressure [OR 1.99 (CI 1.07–3.72), P = 0.03], and abdominal obesity [OR 1.52 (CI 1.01–2.28), P = 0.04]. Plasma polyunsaturated to saturated fat ratio exacerbated these effects; subjects in the lowest 50th percentile had even greater risk of the MetS [OR 4.40 (CI 1.55–12.45), P = 0.005], fasting hyperglycemia, high systolic blood pressure, and abdominal obesity (P < 0.05).
Conclusions:LTA, _TNF_-α, and IL-6 genotype interactions increased MetS risk, which was further exacerbated by a low plasma polyunsaturated to saturated fat exposure, indicating important modulation of genetic risk by dietary fat exposure.
Copyright © 2010 by The Endocrine Society
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