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

Eva-Maria D Nielsen; Lars Hansen; Søren Morgenthaler Echwald; Thomas Drivsholm; Knut Borch-Johnsen; Claus Thorn Ekstrøm; Torben Hansen; Oluf Pedersen

doi:10.1097/01.fpc.0000054105.48725.5c

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

Eva-Maria D Nielsen, Lars Hansen, Søren Morgenthaler Echwald, Thomas Drivsholm, Knut Borch-Johnsen, Claus Thorn Ekstrøm, Torben Hansen, Oluf Pedersen

Afdeling for Almen Medicin

19 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Pharmacogenetics and Genomics
Vol/bind	13
Udgave nummer	7
Sider (fra-til)	417-23
Antal sider	7
ISSN	1744-6872
DOI	https://doi.org/10.1097/01.fpc.0000054105.48725.5c
Status	Udgivet - 2003

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10.1097/01.fpc.0000054105.48725.5c

Citationsformater

Nielsen, E.-M. D., Hansen, L., Echwald, S. M., Drivsholm, T., Borch-Johnsen, K., Ekstrøm, C. T., Hansen, T., & Pedersen, O. (2003). Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects. Pharmacogenetics and Genomics, 13(7), 417-23. https://doi.org/10.1097/01.fpc.0000054105.48725.5c

Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects. / Nielsen, Eva-Maria D; Hansen, Lars; Echwald, Søren Morgenthaler et al.
I: Pharmacogenetics and Genomics, Bind 13, Nr. 7, 2003, s. 417-23.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Nielsen, E-MD, Hansen, L, Echwald, SM, Drivsholm, T, Borch-Johnsen, K, Ekstrøm, CT, Hansen, T & Pedersen, O 2003, 'Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects', Pharmacogenetics and Genomics, bind 13, nr. 7, s. 417-23. https://doi.org/10.1097/01.fpc.0000054105.48725.5c

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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.",

keywords = "Adult, Aged, Alleles, Blood Glucose, Body Constitution, Case-Control Studies, DNA Mutational Analysis, Denmark, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Gene Frequency, Genetic Variation, Glucose Tolerance Test, Heterozygote, Humans, Insulin, Male, Middle Aged, Point Mutation, Polymorphism, Genetic, Receptors, Cytoplasmic and Nuclear, Transcription Factors, Triglycerides, Valine",

author = "Nielsen, {Eva-Maria D} and Lars Hansen and Echwald, {S{\o}ren Morgenthaler} and Thomas Drivsholm and Knut Borch-Johnsen and Ekstr{\o}m, {Claus Thorn} and Torben Hansen and Oluf Pedersen",

year = "2003",

doi = "10.1097/01.fpc.0000054105.48725.5c",

language = "English",

volume = "13",

pages = "417--23",

journal = "Pharmacogenetics and Genomics",

issn = "1744-6872",

publisher = "Lippincott Williams & Wilkins",

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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

SN - 1744-6872

VL - 13

SP - 417

EP - 423

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

IS - 7

ER -

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

Abstract

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