SLCO1B1 Gene Variants and Urine Arsenic Metabolites in the Strong Heart Family Study

Abstract

Background. Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases, and these patterns have often been interpreted as a measure of arsenic metabolism. However, other processes affecting toxicokinetics may influence urine arsenic species patterns. The transporter coded by SLCO1B1 has been shown to transport arsenic species in HEK-293 cells, but human population studies are lacking. Aims. To evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study (SHFS). Methods. Arsenic species were measured by anion-exchange HPLC-ICPMS, and % arsenic species biomarkers were calculated as the (%) contribution of inorganic arsenic, monomethylarsonate (MMA) and dimethylarsinate (DMA) to their sum. We estimated associations between % arsenic species and 5 SNPs in the SLCO1B1 gene in 157 participants from 5 families. Linear regression models for the minor allele dose at each SNP accounted for kinships and were adjusted for sex, body mass index and study center. Results. The C 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 C/C genotype frequency was 17% and the C/G genotype frequency was 43% at rs1564370. The A 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 rs2291075 A/A genotype frequency was 1% and A/G genotype frequency was 15%. These two SNPs had correlation r = 0.42. Conclusions. Common variants in SLCO1B1 were associated with differences in urine arsenic species patterns in a candidate gene study. This may suggest that the % arsenic species interpreted as “arsenic metabolism” biomarkers reflect arsenic toxicokinetics more broadly. Replication of this finding in other populations and analyses with arsenic-related disease outcomes are needed.