Abstract
Background and objectives
ATP-binding cassette transporter 1 (ABCA1) is a trans-membrane protein responsible for the efflux of cholesterol and phospholipids
across the cell membrane, an essential step in the reverse cholesterol transport system.
This study investigates the effect of five non-synonymous SNPs of ABCA1 gene on plasma HDL-C levels in Pakistani individuals free of ischemic heart disease
and stroke.
Methods
Five non-synonymous SNPs were selected after sequencing ABCA1 gene in patients of Hypoalphalipoproteinemia. The presence of these SNPs was then
checked in 200 individuals by using PCR-RFLP. Plasma glucose and lipid fractions were
measured in fasting state. Ethical approval was obtained from the Ethical Review Committee,
Aga Khan University and informed consent was obtained from all subjects.
Results
LL genotype of V825L polymorphism was associated with decreased levels of HDL-C [−0.17 (−0.32 to −0.19); P=0.02] and P774 allele showed a significant increase in HDL-C levels as compared to
T774 allele [−0.15 (−0.18 to −0.02); P=0.01]. R219K, A399V and V771M polymorphisms did not show any association with levels
of HDL-C, LDL-C, cholesterol and triglycerides. Haplotype analysis between R219K and
V825L polymorphisms showed a unique interaction between R219 allele and L825 allele.
The RL haplotype was found to be associated with decreased levels of HDL-C [−0.12 (−0.22 to −0.03); P=0.001].
Conclusions
ABCA1 polymorphisms are associated with varying levels of HDL-C in Pakistani individuals.
These results warrant further investigations as ABCA1 polymorphisms may have a major role in the high incidence of cardiovascular disorders
in South Asians.
Keywords
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Article info
Publication history
Published online: June 24, 2006
Accepted:
December 7,
2005
Received in revised form:
November 29,
2005
Received:
September 30,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
