SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study.

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Citation: Toxicological Sciences. 136(1):19-25, 2013 Nov.PMID: 23970802Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Multicenter Study | Research Support, N.I.H., ExtramuralSubject headings: *Arsenic/ur [Urine] | *Cardiovascular Diseases/eh [Ethnology] | *Indians, North American/ge [Genetics] | *Organic Anion Transporters/ge [Genetics] | *Organic Anion Transporters/me [Metabolism] | *Polymorphism, Single Nucleotide | *Water Pollutants, Chemical/ur [Urine] | Arsenicals/ur [Urine] | Biological Markers/ur [Urine] | Biotransformation | Cacodylic Acid/ur [Urine] | Female | Gene Frequency | Genetic Association Studies | Heterozygote | Homozygote | Humans | Linear Models | Male | Phenotype | Prospective Studies | United States/ep [Epidemiology]Year: 2013ISSN:
  • 1096-0929
Name of journal: Toxicological sciences : an official journal of the Society of ToxicologyAbstract: Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases. The organic anion transporter coded by the gene SLCO1B1 may transport arsenic species, but its association with arsenic metabolites in human urine has not yet been studied. The objective of this study is to evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study. 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. The minor allele of rs1564370 was associated with lower %MMA (p = .0003) and higher %DMA (p = .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 = .0006) and higher %DMA (p = .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 was 15%. 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.All authors: Cole SA, Cropp CD, Fallin MD, Francesconi KA, Goessler W, Gribble MO, Haack K, Kao WH, Laston SL, Maccluer JW, Navas-Acien A, Silbergeld EK, Umans JG, Voruganti VSFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2014-08-21
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Journal Article MedStar Authors Catalog Article 23970802 Available 23970802

Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases. The organic anion transporter coded by the gene SLCO1B1 may transport arsenic species, but its association with arsenic metabolites in human urine has not yet been studied. The objective of this study is to evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study. 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. The minor allele of rs1564370 was associated with lower %MMA (p = .0003) and higher %DMA (p = .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 = .0006) and higher %DMA (p = .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 was 15%. 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.

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