title: SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study.
abstract: 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.
authors: * Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205;
authors: Matthew O
authors: MO
authors: Gribble
authors: Venkata Saroja
authors: VS
authors: Voruganti
authors: Cheryl D
authors: CD
authors: Cropp
authors: Kevin A
authors: KA
authors: Francesconi
authors: Walter
authors: W
authors: Goessler
authors: Jason G
authors: JG
authors: Umans
authors: Ellen K
authors: EK
authors: Silbergeld
authors: Sandra L
authors: SL
authors: Laston
authors: Karin
authors: K
authors: Haack
authors: Wen Hong Linda
authors: WH
authors: Kao
authors: Margaret Daniele
authors: MD
authors: Fallin
authors: Jean W
authors: JW
authors: Maccluer
authors: Shelley A
authors: SA
authors: Cole
authors: Ana
authors: A
authors: Navas-Acien
mesh_terms: D001151:Arsenic / Q000652:urine*; D001152:Arsenicals / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D002101:Cacodylic Acid / Q000652:urine; D002318:Cardiovascular Diseases / Q000208:ethnology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D016014:Linear Models; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014481:United States / Q000453:epidemiology; D014874:Water Pollutants, Chemical / Q000652:urine*
chemical_list: D001152:Arsenicals; D015415:Biomarkers; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D014874:Water Pollutants, Chemical; D002101:Cacodylic Acid; C020300:monomethylarsonic acid; D001151:Arsenic
keywords: American Indians; OATPC; SLCO1B1; Strong Heart Study.; arsenic metabolism; arsenic species
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