ABCMdb

PMID: 23770371

Lin JY, Zhang M, Schatton T, Wilson BJ, Alloo A, Ma J, Qureshi AA, Frank NY, Han J, Frank MH
Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk.
Biochem Biophys Res Commun. 2013 Jul 5;436(3):536-42. doi: 10.1016/j.bbrc.2013.06.006. Epub 2013 Jun 12., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCB5 p.Val115Glu Twelve human melanoma cell lines were genotyped for the rs2301641 SNP, which encodes a non-synonymous ABCB5 amino acid change (K115E). Login to comment 7 ABCB5 p.Val115Glu Our results identify novel associations of the ABCB5 K115E polymorphism with human pigmentation phenotype and melanoma risk and point to potential functional roles of ABCB5 in melanomagenesis. Login to comment 30 ABCB5 p.Val115Glu Among single nucleotide polymorphisms (SNPs) of the ABCB5 gene, several, including the rs2301641 SNP, which encodes a non-synonymous ABCB5 amino acid change (K115E), have been predicted to be relevant to ABCB5 function based on bioinformatic analyses [17]. Login to comment 34 ABCB5 p.Val115Glu We confirmed the direct association of one of these SNPs, rs2301641 (K115E), with ABCB5 function and, furthermore, uncovered a novel association of ABCB5 with pigmentation. Login to comment 112 ABCB5 p.Val115Glu 3.5. Association between rs2301641 genotype and ABCB5-mediated Rh-123 efflux capacity The SNP rs2301641 encodes a non-synonymous ABCB5 amino acid change (K115E). Login to comment 126 ABCB5 p.Val115Glu Importantly, evaluation of relative Rh-123 efflux capacities in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) revealed that the SNP allele G (Glu [E]) was associated with markedly lower, 89%-reduced Rh-123 efflux capacity compared to the SNP allele A (Lys [K]) (P < 0.01, Fig. 3A). Login to comment 128 ABCB5 p.Val115Glu 3.6. Association between rs2301641 genotype and pigmentation Given the additional association of the rs2301641 ABCB5 SNP with non-red compared to red hair color (OR: 0.38, 95% CI: 0.141.03) in control subjects, we measured melanin concentration, a measure of pigmentation, in eleven human melanoma cell lines genotyped for this SNP (K115E). Login to comment 134 ABCB5 p.Val115Glu (A) Relative Rh-123 efflux capacities in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; // P < 0.01). Login to comment 135 ABCB5 p.Val115Glu ABCB5 p.Val115Glu (B) Relative pigmentation in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; / P < 0.05). Login to comment 136 ABCB5 p.Val115Glu (B) Relative pigmentation in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; / P < 0.05). Login to comment 137 ABCB5 p.Val115Glu Discussion In this study, we have identified three SNPs of the ABCB5 gene associated with melanoma risk, and shown for one SNP (rs2301641), which encodes a non-synonymous ABCB5 amino acid change (K115E), that the variant genotype that confers decreased melanoma risk is associated with lower ABCB5 protein function. Login to comment 138 ABCB5 p.Val115Glu Discussion In this study, we have identified three SNPs of the ABCB5 gene associated with melanoma risk, and shown for one SNP (rs2301641), which encodes a non-synonymous ABCB5 amino acid change (K115E), that the variant genotype that confers decreased melanoma risk is associated with lower ABCB5 protein function. Login to comment 141 ABCB5 p.Val115Glu Bioinformatic in silico analyses of ABCB5 gene polymorphisms had previously predicted the K115E amino acid substitution encoded by the rs2301641 SNP, which changes a positively charged amino acid to a negatively charged one and localizes to an extracellular loop of the ABCB5 protein [4], to be potentially deleterious to ABCB5 molecular function [17], a notion now for the first time experimentally supported by our study. Login to comment 142 ABCB5 p.Val115Glu Bioinformatic in silico analyses of ABCB5 gene polymorphisms had previously predicted the K115E amino acid substitution encoded by the rs2301641 SNP, which changes a positively charged amino acid to a negatively charged one and localizes to an extracellular loop of the ABCB5 protein [4], to be potentially deleterious to ABCB5 molecular function [17], a notion now for the first time experimentally supported by our study. Login to comment