Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort |
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| Authors: | Nieters Alexandra Becker Nikolaus Linseisen Jakob |
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| Institution: | (1) German Cancer Research Center, Division of Clinical Epidemiology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. a.nieters@dkfz.de, DE;(2) Unit of Human Nutrition and Cancer Prevention, Technical University of Munich, Munich, Germany, DE |
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| Abstract: | Summary. Background, aim: In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms
have been reported which possibly modify human obesity risk. The aim of this study was a) to reproduce these observations
with data and biological material from the Heidelberg cohort of EPIC, a large European prospective investigation into diet
and cancer, and b) to investigate potential effects of interactions between dietary fatty acid intake and allelic variants
on obesity risk. Subjects and methods: Within EPIC-Heidelberg, 154 subjects with a body mass index > 35 kg/m2 and 154 age- and sex-matched normal-weight controls were selected and genotypes determined for 11 candidate genes. Dietary
intake was assessed by a validated food frequency questionnaire. Odds ratios (OR) were computed by means of unconditional
logistic regression and different adjustment models. Genotyping was performed by PCR-RFLP and allele-specific PCR. Results: For most of the investigated genes (PPARA, PPARG2, UCP1, UCP2, UCP3, BAR-2, APM1, leptin, SORBS1, HSL, and TNFA) an indication
for a minor effect on obesity risk was found. Indication of a risk-increasing effect was strongest for the homozygous form
of leptin −2548AA with an adjusted OR of 3.53 (p < 0.009). Additionally, for the polymorphic sites of BAR-2 (Arg16Gly and
Gln27Glu) a significant effect on obesity risk was seen. Importantly, the results of the analysis of gene-diet interactions
suggest that the allelic variants of candidate genes (leptin, TNFA, PPARG2) might strongly affect diet-related obesity risk.
Conclusions: The results support some but not all previous reports about a risk-modulating effect of polymorphisms in genes affecting
obesity risk. The most important finding is an indication of substantial interaction between allelic variants of particular
genes and fatty acid intake-related obesity risk. These observations suggest that future studies on polymorphisms in obesity
genes should take data on dietary habits into account.
Received: 3 May 2002, Accepted: 21 August 2002
Correspondence to: Dr. A. Nieters |
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| Keywords: | EPIC – obesity – gene polymorphisms – fatty acids – gene-diet interaction |
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