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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, Endocrinology, Volume 151, Issue 2, 1 February 2010, Page 840, https://doi.org/10.1210/endo.151.2.9997
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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).