PMID- 16684361
OWN - NLM
STAT- MEDLINE
DCOM- 20060929
LR  - 20211020
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 7
DP  - 2006 May 10
TI  - Nucleotide sequence analyses of the MRP1 gene in four populations suggest 
      negative selection on its coding region.
PG  - 111
AB  - BACKGROUND: The MRP1 gene encodes the 190 kDa multidrug resistance-associated 
      protein 1 (MRP1/ABCC1) and effluxes diverse drugs and xenobiotics. Sequence 
      variations within this gene might account for differences in drug response in 
      different individuals. To facilitate association studies of this gene with 
      diseases and/or drug response, exons and flanking introns of MRP1 were screened 
      for polymorphisms in 142 DNA samples from four different populations. RESULTS: 
      Seventy-one polymorphisms, including 60 biallelic single nucleotide polymorphisms 
      (SNPs), ten insertions/deletions (indel) and one short tandem repeat (STR) were 
      identified. Thirty-four of these polymorphisms have not been previously reported. 
      Interestingly, the STR polymorphism at the 5' untranslated region (5'UTR) occurs 
      at high but different frequencies in the different populations. Frequencies of 
      common polymorphisms in our populations were comparable to those of similar 
      populations in HAPMAP or Perlegen. Nucleotide diversity indices indicated that 
      the coding region of MRP1 may have undergone negative selection or recent 
      population expansion. SNPs E10/1299 G>T (R433S) and E16/2012 G>T (G671V) which 
      occur at low frequency in only one or two of four populations examined were 
      predicted to be functionally deleterious and hence are likely to be under 
      negative selection. CONCLUSION: Through in silico approaches, we identified two 
      rare SNPs that are potentially negatively selected. These SNPs may be useful for 
      studies associating this gene with rare events including adverse drug reactions.
FAU - Wang, Zihua
AU  - Wang Z
AD  - Department of Biochemistry, National University of Singapore, Singapore. 
      g0202483@nus.edu.sg
FAU - Sew, Pui-Hoon
AU  - Sew PH
FAU - Ambrose, Helen
AU  - Ambrose H
FAU - Ryan, Stephen
AU  - Ryan S
FAU - Chong, Samuel S
AU  - Chong SS
FAU - Lee, Edmund J D
AU  - Lee EJ
FAU - Lee, Caroline G L
AU  - Lee CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060510
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Databases, Genetic
MH  - Exons/genetics
MH  - Haplotypes
MH  - Humans
MH  - Multidrug Resistance-Associated Proteins/*genetics
MH  - Open Reading Frames/*genetics
MH  - Polymorphism, Genetic/*genetics
MH  - Population Groups/*genetics
MH  - *Selection, Genetic
MH  - Sequence Analysis, DNA
MH  - Trinucleotide Repeat Expansion/genetics
PMC - PMC1488846
EDAT- 2006/05/11 09:00
MHDA- 2006/09/30 09:00
PMCR- 2006/05/10
CRDT- 2006/05/11 09:00
PHST- 2006/02/07 00:00 [received]
PHST- 2006/05/10 00:00 [accepted]
PHST- 2006/05/11 09:00 [pubmed]
PHST- 2006/09/30 09:00 [medline]
PHST- 2006/05/11 09:00 [entrez]
PHST- 2006/05/10 00:00 [pmc-release]
AID - 1471-2164-7-111 [pii]
AID - 10.1186/1471-2164-7-111 [doi]
PST - epublish
SO  - BMC Genomics. 2006 May 10;7:111. doi: 10.1186/1471-2164-7-111.