Document Detail


Relationships between common polymorphisms of adenosine triphosphate-binding cassette transporter A1 and high-density lipoprotein cholesterol and coronary heart disease in a population with type 2 diabetes mellitus.
MedLine Citation:
PMID:  19059534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with type 2 diabetes mellitus (T2D) have a high coronary risk partly because of low levels of high-density lipoprotein-cholesterol (HDL-C). The adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays a key role in HDL metabolism. We studied the association of common single nucleotide polymorphisms (SNPs) in the ABCA1 gene with HDL-C levels and coronary risk in a cohort of subjects with T2D. We studied 5 SNPs: +69C>T, +378G>C, R219K, I883M, and R1587K. The C allele of +378G>C was significantly associated with lower HDL-C concentrations (P = .04); and the M allele of I883M, with higher HDL-C concentrations (P = .03). No significant association was found between these SNPs and the incidence of new coronary events. Nevertheless, cross-sectional data on entry showed that the frequency of K219 was lower in patients with previous coronary heart disease (angina pectoris and/or myocardial infarction) (odds ratio, OR [95% confidence interval, CI] = 0.80 [0.65-0.98], P = .03, after adjustment for multiple risk factors other than HDL-C). The frequency of K1587 was higher in patients with angina pectoris (OR [95% CI] = 1.27 [1.01-1.58], P = .04, after multiple adjustment). The TT genotype of the C69T SNP was less frequent in subjects with prior myocardial infarction (OR [95% CI] = 0.28 [0.13-0.61], P = .001, after multiple adjustment). These associations persisted after further adjustment for HDL-C levels. In conclusion, common genetic variations of ABCA1 had a moderate influence on HDL-C levels and/or coronary heart disease in patients with T2D. These 2 effects were independent.
Authors:
Isabelle Porchay-Baldérelli; Franck Péan; Nathalie Emery; Suliya Maimaitiming; Naima Bellili; Florence Travert; Kamel Mohammedi; Ronan Roussel; Michel Marre; Frédéric Fumeron;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  58     ISSN:  1532-8600     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-08     Completed Date:  2009-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  74-9     Citation Subset:  IM    
Affiliation:
INSERM U695, Genetic Determinants for Type 2 Diabetes and its Vascular Complications, Xavier Bichat Medical School, 16 rue Henri Huchard, 75018 Paris, France.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics*
Aged
Alleles
Cholesterol, HDL / blood*
Cohort Studies
Coronary Disease / blood*,  complications,  genetics*
Cross-Sectional Studies
DNA / chemistry,  genetics
Diabetes Mellitus, Type 2 / blood*,  complications,  genetics*
Female
Genotype
Humans
Logistic Models
Male
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Prevalence
Prospective Studies
Randomized Controlled Trials as Topic
Chemical
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL; 9007-49-2/DNA
Investigator
Investigator/Affiliation:
M Marre / ; G Schernthaner / ; R Rottiers / ; V Profozic / ; J Perusicova / ; M Marre / ; J Mann / ; S Pappas / ; G Pogatsa / ; J Belkhadir / ; F Hakkou / ; J Jonker / ; G Schernthaner / ; F Hawkins / ; K Scheidegger / ; M Gueddiche / ; U Gorpe / ; G C Viberti / ; F Alhenc-Gelas / ; J P Boissel / ; F Cambien / ; S Etienne / ; A Girault-Louvel / ; P Gueret / ; M Lièvre / ; J Mann / ; M Marre / ; J Ménard / ; P Passa / ; P F Plouin / ; D Vasmant / ; L Vaur / ; G C Viberti / ; C Weisselberg / ; J P Boissel / ; M Lièvre / ; V Bost / ; M Cambien / ; Y Gallois / ; N Genes / ; J Gillet / ; M Hervé / ; M Lièvre / ; M Marre / ; L Martin / ; A Perret-Hantzperg / ; P F Plouin / ; L Vaur / ; F Alhenc-Gelas / ; F Cambien / ; A Girault-Louvel / ; M Lièvre / ; M Marre / ; J Ménard / ; E Bonnefoy / ; G Chatellier / ; T Moreau / ; L Pinède / ; E Eschwege / ; C E Mogensen / ; N Victor / ; S Weber /

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