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

Section of General Practice

19 Citations (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.

Original language	English
Journal	Pharmacogenetics and Genomics
Volume	13
Issue number	7
Pages (from-to)	417-23
Number of pages	7
ISSN	1744-6872
DOIs	https://doi.org/10.1097/01.fpc.0000054105.48725.5c
Publication status	Published - 2003

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/01.fpc.0000054105.48725.5c

Cite this

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.
In: Pharmacogenetics and Genomics, Vol. 13, No. 7, 2003, p. 417-23.

Research output: Contribution to journal › Journal article › Research › 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, vol. 13, no. 7, pp. 417-23. https://doi.org/10.1097/01.fpc.0000054105.48725.5c

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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.",

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

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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

Keywords

UN SDGs

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