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HERO ID
1936044
Reference Type
Journal Article
Title
SLCO1B1 variants and urine arsenic metabolites in the strong heart family study
Author(s)
Gribble, MO; Voruganti, VS; Cropp, CD; Francesconi, KA; Goessler, W; Umans, JG; Silbergeld, EK; Laston, SL; Haack, K; Kao, WHL; Fallin, MD; MacCluer, JW; Cole, SA; Navas-Acien, A
Year
2013
Is Peer Reviewed?
1
Journal
Toxicological Sciences
ISSN:
1096-6080
EISSN:
1096-0929
Volume
136
Issue
1
Page Numbers
19-25
Language
English
PMID
23970802
DOI
10.1093/toxsci/kft181
Web of Science Id
WOS:000327458600003
URL
https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kft181
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Abstract
Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases. The organic anion transporter gene SLCO1B1 may transport arsenic species, but its association with arsenic metabolites in human urine has not yet been studied.Objective. To evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study (SHFS).Methods. We estimated associations between % arsenic species biomarker traits and 5 single-nucleotide polymorphisms (SNPs) in the SLCO1B1 gene in 157 participants, assuming additive genetics. Linear regression models for each SNP accounted for kinships and were adjusted for sex, body mass index and study center.Results. The minor allele of rs1564370 was associated with lower %MMA (p = 0.0003) and higher %DMA (p = 0.0002), accounting for 8% of the variance for %MMA and 9% for %DMA. The rs1564370 minor allele homozygote frequency was 17% and the heterozygote frequency was 43%. The minor allele of rs2291075 was associated with lower %MMA (p = 0.0006) and higher %DMA (p = 0.0014), accounting for 7% of the variance for %MMA and 5% for %DMA. The frequency of rs2291075 minor allele homozygotes was 1% and of heterozygotes it was 15%.Conclusions. Common variants in SLCO1B1 were associated with differences in arsenic metabolites in a preliminary candidate gene study. Replication of this finding in other populations and analyses with respect to disease outcomes are needed to determine whether this novel candidate gene is important for arsenic-associated disease risks.
Keywords
American Indians; arsenic metabolism; arsenic species; SLCO1B1; OATPC; Strong Heart Study
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