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    
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.
Myrna Mantaring; Jeffrey Rhyne; Seung Ho Hong; Michael Miller
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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    
Department of Medicine, University of Maryland Medical Center and VA Maryland Health Care System, Baltimore, MD, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics*
Cholesterol, HDL / blood*
Cohort Studies
Gene Frequency
Genetic Variation*
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphism, Single-Stranded Conformational
Grant Support
Reg. No./Substance:
0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, HDL

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