ABCMdb

PMID: 16684361

Wang Z, Sew PH, Ambrose H, Ryan S, Chong SS, Lee EJ, Lee CG
Nucleotide sequence analyses of the MRP1 gene in four populations suggest negative selection on its coding region.
BMC Genomics. 2006 May 10;7:111., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC1 p.Gly671Val ABCC1 p.Arg433Ser 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. Login to comment 45 ABCC1 p.Gly671Val ABCC1 p.Arg433Ser We found that SNPs E10/1299G>T, which resulted in arginine-serine substitution at amino acid position 433 (R433S) and E16/2012G>T, which resulted in glycine-valine substitution at amino acid position 671 (G671V), may potentially adversely affect the function of MRP1. Login to comment 120 ABCC1 p.Thr73Ile B A C SNPe1* SNPe2 SNPe3 SNPe4 SNPe5 SNPe6* SNPe7 SNPe8 SNPe9* SNPe10 SNPe11 SNPe12* SNPe13* SNPe14 SNPe15 SNPe16* SNPe17 SNPe18 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 mRNA of ABCC1 CH ML IN CAU SNPe1* E2/218 C>T T73I 0.65 benign - 1.39 2.86 0 0 SNPe2 E6/651 G>A - - - 0 0 2.86 0 SNPe3 E8/816 G>A - - - 2.78 0 0 0 Oselin et al. Login to comment 123 ABCC1 p.Arg433Ser 2000 SNPe6* E10/1299 G>T R433S 0.12 benign -3.59003 0 0 0 1.39 Conrad et al . Login to comment 125 ABCC1 p.Arg633Gln 2003 SNPe8 E13/1704 C>T - - - 0 0 4.29 1.39 SNPe9* E14/1898 G>A R633Q 0.59 benign -0.6953 0 0 0 1.39 Le Saux et al . Login to comment 127 ABCC1 p.Gly671Val 2000 SNPe11 E16/2007 C>T - - - 1.39 0 0 0 SNPe12* E16/2012 G>T G671V 0.00** probably damaging -3.50442 0 0 1.43 2.78 Conrad et al . Login to comment 129 ABCC1 p.Arg723Gln 2000 SNPe13* E17/2168 G>A R723Q 0.36 benign -1.12171 0 2.86 0 0 Moriya et al . Login to comment 130 ABCC1 p.Thr884Met 2002 SNPe14 E17/2217 C>T - - - 0 0 1.43 0 SNPe15 E17/2268 G>A - - - 1.39 0 0 0 SNPe16* E20/2651 C>T T884M 0.13 benign - 0 1.43 0 0 SNPe17 E21/2793 C>T - - - 0 0 1.43 0 SNPe18 E28/4002 G>A - - - 8.33 7.14 20.00 37.50 Oselin et al. Login to comment 147 ABCC1 p.Gly671Val Significantly, all of the three different algorithms predicted that SNP E16/2012 G>T, which resides close to Walker A and results in G671V substitution, was likely to have a potentially deleterious effect on protein function (Fig. 2C). Login to comment 150 ABCC1 p.Gly671Val The lower expression of the MRP1 G671V transcript is suggestive of greater accumulation of MRP1 drugs in the cells which may lead to adverse drug reactions. Login to comment 151 ABCC1 p.Gly671Val Curiously, that report also found that the G671V polymorphism did not affect the transport of MRP1 substrates including leukotriene C4, 17β-estradiol 17β-(D)-glucuronide and estrone sulfate by membrane vesicles prepared from transiently transfected HEKSV293T cells [12]. Login to comment 153 ABCC1 p.Gly671Val The observation that the G671V polymorphism did not affect MRP1 protein expression or transport ability of some MRP1 substrates in vitro [12,51] does not rule out the possibility of functional significance of this polymorphism in vivo especially since the same group reported decreased transcript expression in individuals carrying this polymorphism. Login to comment 156 ABCC1 p.Glu1089Gln It has been reported that an artificial mutation E1089Q created in MRP1 markedly affected the ability of MRP1 protein to confer resistance without affecting its ability to transport organic anions [52]. Login to comment