Atherosclerosis 187 (2006) 309–315 The V227A polymorphism at the PPARA locus is associated with serum lipid concentrations and modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentrations in Chinese women Edmund Chan a , Chuen Seng Tan b , Mabel Deurenberg-Yap c , Kee Seng Chia b , Suok Kai Chew d , E Shyong Tai a,b,∗ a Department of Endocrinology, Singapore General Hospital, Block 6 level 6, Room B35, Outram Road, Singapore 169608, Republic of Singapore b National University of Singapore-Genome Institute of Singapore Centre for Molecular Epidemiology, Singapore, Republic of Singapore c Health Promotion Board, Singapore, Republic of Singapore d Epidemiology and disease Control Division, Ministry of Health, Singapore, Republic of Singapore Received 15 July 2005; received in revised form 2 October 2005; accepted 3 October 2005 Available online 9 November 2005 Abstract Peroxisome proliferators activated receptor  (PPAR) regulates the transcription of several proteins involved in human lipoprotein metabolism. We screened the PPARA locus for polymorphisms in 20 unrelated subjects from each of three ethnic groups (Chinese, Malays and Asian Indians). Only the V227A polymorphism was observed. We genotyped 4248 subjects (2899 Chinese, 761 Malay and 588 Asian Indians) and found allele frequencies for the A227 allele of 0.04 in Chinese, 0.006 in Malays and 0.003 in Asian Indians. We examined the associations between this polymorphism and serum lipid concentrations in Chinese. In women, but not in men, the presence of the A227 allele was associated with lower serum concentrations of total cholesterol [5.38 mmol/l (95%CI: 5.22–5.54) versus 5.21 mmol/l (95%CI: 4.99–5.43), p = 0.047] and triglycerides [1.19 mmol/l (95%CI: 1.10–1.28) versus 1.09 mmol/l (95%CI: 0.98–1.21), p = 0.048]. We also found that the V227A polymorphism modulates the association between dietary polyunsaturated fatty acid intake and serum high density lipoprotein concentration (p-value for interaction = 0.049). Our findings implicate PPAR in the lipid lowering associated with diets high in PUFA and suggests that genetic variation at the PPARA locus may determine the lipid response to changes in PUFA intake. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Perosixome proliferator activated receptor ; Polyunsaturated fatty acids; Polymorphism; Lipids; Gene–nutrient interaction 1. Introduction Peroxisome proliferator activated receptor  (PPAR) is a ligand-activated receptor transcription factor belonging to the nuclear receptor superfamily. The gene (PPARA) encod- ing PPAR is located on the long arm of chromosome 22. PPAR is highly expressed in liver, kidney, heart and muscle, and in cells of the arterial wall. In these tissues, it modu- lates the transcription of key proteins involved in lipid and ∗ Corresponding author. Tel.: +65 6321 4654; fax: +65 6227 3576. E-mail address: eshyong@pacific.net.sg (E.S. Tai). glucose metabolism, the inflammatory response and energy homeostasis [1]. The PPARA locus is polymorphic in humans. Several of these polymorphisms have been associated with variation in obesity, serum lipid concentrations and coronary artery disease [2–8]. PPAR-mediated transcriptional regulation of target genes is tightly controlled by ligand activation. Activated PPARs heterodimerize with the retinoid X receptor (RXR), bind to DNA and modulate gene transcription. Various natu- ral and synthetic PPAR ligands are known to regulate genes through the activation of PPAR. For example, fibrates are known ligands for PPAR and the transcriptional regulation 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.10.002