TY - JOUR

T1 - Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects

AU - Nielsen, Eva-Maria D

AU - Hansen, Lars

AU - Echwald, Søren Morgenthaler

AU - Drivsholm, Thomas

AU - Borch-Johnsen, Knut

AU - Ekstrøm, Claus Thorn

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Alleles

KW - Blood Glucose

KW - Body Constitution

KW - Case-Control Studies

KW - DNA Mutational Analysis

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Fasting

KW - Female

KW - Gene Frequency

KW - Genetic Variation

KW - Glucose Tolerance Test

KW - Heterozygote

KW - Humans

KW - Insulin

KW - Male

KW - Middle Aged

KW - Point Mutation

KW - Polymorphism, Genetic

KW - Receptors, Cytoplasmic and Nuclear

KW - Transcription Factors

KW - Triglycerides

KW - Valine

U2 - 10.1097/01.fpc.0000054105.48725.5c

DO - 10.1097/01.fpc.0000054105.48725.5c

M3 - Journal article

C2 - 12835617

VL - 13

SP - 417

EP - 423

JO - Pharmacogenetics

JF - Pharmacogenetics

SN - 1744-6872

IS - 7

ER -