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.
BACKGROUND
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.


METHODS
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.
Phillips
Catherine M
CM
Nutrigenomics Research Group, University College Dublin School of Public Health and Population Science, University College Dublin Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Goumidi
Louisa
L
Bertrais
Sandrine
S
Ferguson
Jane F
JF
Field
Martyn R
MR
Kelly
Enda D
ED
Mehegan
John
J
Peloso
Gina M
GM
Cupples
L Adrienne
LA
Shen
Jian
J
Ordovas
Jose M
JM
McManus
Ross
R
Hercberg
Serge
S
Portugal
Henri
H
Lairon
Denis
D
Planells
Richard
R
Roche
Helen M
HM
D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004041:Dietary Fats; D005227:Fatty Acids / Q000097:blood*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055105:Waist Circumference
D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein