title: Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects.
abstract: The aim of the study was to investigate whether genetic variation in the peroxisome proliferator-activated receptor-alpha (PPARalpha) is associated with type 2 diabetes and altered lipid or carbohydrate metabolism in glucose tolerant subjects. Mutation analyses of PPARalpha were performed in 56 type 2 diabetic patients. Six variants were identified: IVS3 + 76T>C, IVS3-19C>T, IVS4 + 35C>T, Leu162Val, Arg178Gly and Ala268Val. In a case-control study comprising 738 type 2 diabetic patients and 524 glucose tolerant subjects, the three exon variants did not show any significant differences in allele frequencies between type 2 diabetic patients and control subjects. The functional Leu162Val polymorphism was further investigated in genotype-phenotype studies involving 340 young, healthy subjects and 502 middle-aged glucose tolerant subjects. The young, healthy subjects who were heterozygous for the Leu162Val variant had, on average, a 20% decrease in fasting serum triglyceride levels (P=0.014). This finding was replicated in middle-aged subjects (P=0.023). The Leu162Val polymorphism was not related to alterations in insulin sensitivity, insulin release or level of glycaemia. In conclusion, the Leu162Val polymorphism of PPARalpha is associated with a decreased level of fasting serum triglyceride in glucose tolerant white subjects.
authors.affiliation: Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Copenhagen, Denmark. emdn@steno.dk
authors.forename: Eva-Maria D
authors.initials: EM
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Søren M
authors.initials: SM
authors.lastname: Echwald
authors.forename: Thomas
authors.initials: T
authors.lastname: Drivsholm
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Claus T
authors.initials: CT
authors.lastname: Ekstrøm
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005215:Fasting; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*; D014633:Valine / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D014633:Valine