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
Author(s)
Lacquemant  C., Lepretre  F., Pineda Torra  I., Manraj  M., Charpentier  G., Ruiz  J., Staels  B., Froguel  P.
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
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 15:16
Last modification date
20/08/2019 15:32
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