Peroxisome proliferator-activated receptor gamma 2 and acyl-CoA synthetase 5 polymorphisms influence diet response.
Peroxisome proliferator-activated receptor gamma (PPARgamma) and its response gene, Acyl CoA synthetase 5 (ACSL5), which has an important role in fatty acid metabolism, may affect weight loss in response to caloric restriction. Therefore, we aimed to determine whether these genes were involved in the interindividual response to dietary treatment. Genotypic/phenotypic comparisons were made between selected obese women from the quintiles losing the most (diet responsive, n = 74) and the quintiles losing the least (diet-resistant, n = 67) weight in the first 6 weeks of a 900-kcal formula diet. Two common PPARgamma single nucleotide polymorphisms, Pro(12)Ala and C1431T, and eight polymorphisms across the ACSL5 gene were selected for single locus and haplotypic association analyses. The PPARgamma Pro(12)Ala single nucleotide polymorphism was associated with diet resistance (odds ratio = 3.48, 95% confidence interval = 1.41 to 8.56, p = 0.03), and the rs2419621, located in the 5'untranslated region of the ACSL5 gene, displayed the strongest association with diet response (odds ratio = 3.45, 95% confidence interval = 1.61 to 7.69, p = 0.001). Skeletal muscle ACSL5 mRNA expression was significantly lower in carriers of the wildtype compared with the variant rs2419621 allele (p = 0.03). Our results suggest a link between PPARgamma2 and ACSL5 genotype and diet responsiveness.
Adamo
Kristi B
KB
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Dent
Robert
R
Langefeld
Carl D
CD
Cox
Miranda
M
Williams
Kathryn
K
Carrick
Kevin M
KM
Stuart
Joan S
JS
Sundseth
Scott S
SS
Harper
Mary-Ellen
ME
McPherson
Ruth
R
Tesson
Frédérique
F
D000704:Analysis of Variance; D003066:Coenzyme A Ligases / Q000235:genetics*; D017931:DNA Primers; D004032:Diet; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D047495:PPAR gamma; D012333:RNA, Messenger; D003066:Coenzyme A Ligases; C485465:ACSL5 protein, human