title: 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.
abstract: Peroxisome proliferators activated receptor alpha (PPARalpha) 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 [5.38mmol/l (95%CI: 5.22-5.54) versus 5.21mmol/l (95%CI: 4.99-5.43), p=0.047] and triglycerides [1.19mmol/l (95%CI: 1.10-1.28) versus 1.09mmol/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 PPARalpha 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.
authors.affiliation: Department of Endocrinology, Singapore General Hospital, Block 6 level 6, Room B35, Outram Road, Singapore 169608, Republic of Singapore.
authors.forename: Edmund
authors.initials: E
authors.lastname: Chan
authors.forename: Chuen Seng
authors.initials: CS
authors.lastname: Tan
authors.forename: Mabel
authors.initials: M
authors.lastname: Deurenberg-Yap
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Suok Kai
authors.initials: SK
authors.lastname: Chew
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005247:Feeding Behavior; D005260:Female; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008019:Life Style; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D011795:Surveys and Questionnaires
chemical_list: D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D008075:Lipoproteins, HDL; D047493:PPAR alpha; D002784:Cholesterol