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This Article Full Text Full Text (PDF) All Versions of this Article: 90/6/1665    most recent ajcn.2009.28101v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Phillips, C. M Articles by Roche, H. M PubMed PubMed Citation Articles by Phillips, C. M Articles by Roche, H. M Agricola Articles by Phillips, C. M Articles by Roche, H. M

Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome^1,2,3

¹ From the Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin, Ireland (CMP, JFF, and HMR); INSERM 476, Lipid Nutrients and Prevention of Metabolic Diseases, INRA 1260, Faculté de Médecine, Université de la Méditerranée, Marseille, France (LG, HP, RP, and DL); INSERM U557, INRA:CNAM, Université Paris 13, Bobigny, France (SB and SH); the Hitachi Dublin Laboratory, Dublin, Ireland (MRF and EDK); Boston University School of Public Health, Boston, MA (GMP and LAC); the Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA (JS and JMO); and the Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland (RM).

² Supported by the European Commission, Framework Programme 6 (LIPGENE) (contract no. FOOD-CT-2003-505944).

³ Address correspondence to HM Roche, Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. E-mail: helen.roche{at}ucd.ie.

Background: Complement component 3 (C3) is a novel determinant of the metabolic syndrome (MetS). Gene-nutrient interactions with dietary fat may affect MetS risk.

Objectives: The objectives were to determine the relation between C3 polymorphisms and MetS and whether interaction with plasma polyunsaturated fatty acids (PUFAs), a biomarker of dietary PUFA, modulate this relation.

Design: C3 polymorphisms (rs11569562, rs2250656, rs1047286, rs2230199, rs8107911, rs344548, rs344550, rs2241393, rs7257062, rs163913, and rs2230204), biochemical measurements, and plasma fatty acids were measured in the LIPGENE–SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study in MetS cases and matched controls (n = 1754).

Results: Two single nucleotide polymorphisms were associated with MetS. rs11569562 GG homozygotes had decreased MetS risk compared with minor A allele carriers [odds ratio (OR): 0.53; 95% CI: 0.35, 0.82; P = 0.009], which was augmented by high plasma PUFA status (OR: 0.32; 95% CI: 0.11, 0.93; P = 0.04). GG homozygotes had lower C3 concentrations than those in AA homozygotes (P = 0.03) and decreased risk of hypertriglyceridemia compared with A allele carriers (OR: 0.54; 95% CI: 0.34, 0.92; P = 0.02), which was further ameliorated by an increase in long-chain n–3 (omega-3) PUFAs (OR: 0.46; 95% CI: 0.22, 0.97; P = 0.04) or a decrease in n–6 PUFAs (OR: 0.32; CI: 0.16, 0.62; P = 0.002). rs2250656 AA homozygotes had increased MetS risk relative to minor G allele carriers (OR: 1.78; CI: 1.19, 2.70; P = 0.02), which was exacerbated by low n–6 PUFA status (OR: 2.20; CI: 1.09, 4.55; P = 0.03).

Conclusion: Plasma PUFAs may modulate the susceptibility to MetS that is conferred by C3 polymorphisms, which suggests novel gene-nutrient interactions. This trial was registered at clinicaltrials.gov as NCT00272428.

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