Mutation screening of the PPARalpha gene in type 2 diabetes associated with coronary heart disease
Details
Serval ID
serval:BIB_BDE0B45C9164
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mutation screening of the PPARalpha gene in type 2 diabetes associated with coronary heart disease
Journal
Diabetes and Metabolism
ISSN
1262-3636
Publication state
Published
Issued date
11/2000
Volume
26
Number
5
Pages
393-401
Notes
20569045
1262-3636
Journal Article --- Old month value: Nov --- Old uritopublisher value: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11119019
1262-3636
Journal Article --- Old month value: Nov --- Old uritopublisher value: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11119019
Abstract
The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPARalpha plays a key role in lipid and glucose metabolism, inflammatory response and energy homeostasis. The aim of our study was to screen the PPARalpha gene for mutations, and to test the genetic contribution of PPARalpha in diabetes and its vascular complications. The first two non coding exons and the coding region of the PPARalpha gene were screened by single strand conformation polymorphism (SSCP) and sequencing in 74 unrelated Type 2 diabetic patients with history of coronary heart disease (CHD) (18 Caucasian and 56 Indian subjects). A total of 7 nucleotide variants were detected: two single amino acid substitutions, a silent mutation, four intron base changes. Association studies were undertaken in two populations of Type 2 diabetic patients from Pondichery and from France, to test the distribution of allelic frequencies for L162V (exon 5) and A268V (exon 7) polymorphisms. No association was found between these PPARalpha variants and diabetes or CHD. However, in the Caucasian diabetic male population with CHD, the Val162 allele carriers showed higher concentrations of total cholesterol and Apo B when compared to non-carriers (p =0.01 and p =0.005, respectively). A trend toward elevated concentrations of total cholesterol and Apo B was also observed in the Caucasian diabetic male patients without CHD carrying Val162 allele. In conclusion, it is likely that PPARalpha gene does not have a major role in diabetes and CHD in our populations, although we can not exclude a minor contribution of the PPARalpha gene to the risk of CHD associated with Type 2 diabetes through a modulation of atherogenic plasma lipids.
Keywords
Amino Acid Substitution
Caucasoid Race
Coronary Disease/complications/*genetics
DNA-Binding Proteins/genetics
Diabetes Mellitus,
Non-Insulin-Dependent/epidemiology/*genetics/physiopathology
Diabetic Angiopathies/*genetics
Female
Genetic Screening
Human
India/ethnology
Male
Mauritius
Middle Age
*Mutation
Polymerase Chain Reaction
*Polymorphism (Genetics)
*Polymorphism, Restriction Fragment Length
Prevalence
Receptors, Cytoplasmic and Nuclear/*genetics
Support, Non-U.S. Gov't
Transcription Factors/*genetics
Variation (Genetics)
Pubmed
Web of science
Create date
03/03/2008 16:16
Last modification date
20/08/2019 16:32