Additive effect of polymorphisms in the IL-6, LTA, and TNF-{alpha} genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components.

Phillips CM, Goumidi L, Bertrais S, Ferguson JF, Field MR, Kelly ED, Mehegan J, Peloso GM, Cupples LA, Shen J, Ordovas JM, McManus R, Hercberg S, Portugal H, Lairon D, Planells R, Roche HM
J Clin Endocrinol Metab. 2010 95 (3): 1386-94

PMID: 20080841 · DOI:10.1210/jc.2009-1081

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-alpha (LTA), TNF-alpha, 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-alpha 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-alpha 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-alpha 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-alpha, 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.

MeSH Terms (18)

Alleles C-Reactive Protein Case-Control Studies Dietary Fats Fatty Acids Genetic Predisposition to Disease Genotype Humans Insulin Interleukin-6 Lymphotoxin-alpha Metabolic Syndrome Polymorphism, Genetic Prospective Studies Regression Analysis Risk Factors Tumor Necrosis Factor-alpha Waist Circumference

Connections (1)

This publication is referenced by other Labnodes entities: