Document Detail


Genotypic variation in ATP-binding cassette transporter-1 (ABCA1) as contributors to the high and low high-density lipoprotein-cholesterol (HDL-C) phenotype.
MedLine Citation:
PMID:  17383594     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ATP-binding cassette transporter-1 (ABCA1) mediates cholesterol efflux and genotypic variation in ABCA1 and may impact reverse cholesterol transport and influence cardiovascular disease (CVD) risk. However, although mutations in ABCA1 have generally been identified with low HDL-C, few have undertaken a comparative evaluation between high and low high-density lipoprotein-cholesterol (HDL-C). Therefore, to evaluate for potential gain-of-function polymorphisms/mutations in ABCA1, 56 consecutive subjects were screened presenting with high (60-99 mg/dL [1.6-2.6 mmol/L]) or very high HDL-C (>100 mg/dL [2.6 mmol/L]) and were compared with subjects with average or low HDL-C (n = 68). Carrier frequencies of common ABCA1 polymorphisms, R219K, V771M, V825I, I883M, E1172D, and R1587K were also assessed. All 50 exons and exon-intron boundaries of ABCA1 were screened using single-stranded conformation polymorphism (SSCP). DNA samples with SSCP-shifts or differing band patterns were sequenced. For the 6 common polymorphisms, genotyping was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Overall, 5 novel nonsynonymous mutations were identified, all of which were associated with low HDL-C. Of the 6 common ABCA1 polymorphisms, very high HDL-C was associated with a higher genotype frequency for R219K (P(trend) = 0.04) and higher genotype and allelic frequency for E1172D (P(trend) = 0.0004, P(trend) = 0.0002, respectively) compared with lower HDL-C. These data reaffirm that rare mutations in ABCA1 are associated with low HDL-C. However, at least 1 ABCA1 polymorphism (eg, E1172D) may contribute to the high HDL-C phenotype.
Authors:
Myrna Mantaring; Jeffrey Rhyne; Seung Ho Hong; Michael Miller
Related Documents :
8767444 - Use of the single strand conformation polymorphism method for rapid screening for mutat...
8018664 - Aging and genetic variation of plasma apolipoproteins. relative loss of the apolipoprot...
15864114 - Genetic and environmental factors affecting the response to statin therapy in patients ...
7989594 - Variation at the hepatic lipase and apolipoprotein ai/ciii/aiv loci is a major cause of...
22527104 - Predisposition gene identification in common cancers by exome sequencing: insights from...
10353384 - Mutations in ras genes in experimental tumours of rodents.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Translational research : the journal of laboratory and clinical medicine     Volume:  149     ISSN:  1931-5244     ISO Abbreviation:  Transl Res     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-04-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101280339     Medline TA:  Transl Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  205-10     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of Maryland Medical Center and VA Maryland Health Care System, Baltimore, MD, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics*
Cholesterol, HDL / blood*
Cohort Studies
Female
Gene Frequency
Genetic Variation*
Genotype
Heterozygote
Humans
Male
Middle Aged
Mutation
Phenotype
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphism, Single-Stranded Conformational
Grant Support
ID/Acronym/Agency:
HL-61369/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Hemoglobin A1c (HbA1c) predicts future drug treatment for diabetes mellitus: a follow-up study using...
Next Document:  Cleavage of E-cadherin: a mechanism for disruption of the intestinal epithelial barrier by Candida a...