Polymorphisms in the organic anion transporting polypeptide genes influence liver parenchymal enhancement in gadoxetic acid-enhanced MRI

Pharmacogenomics. 2013 Oct;14(13):1573-82. doi: 10.2217/pgs.13.132.

Abstract

Aim: This study aimed to investigate whether genetic polymorphisms of the organic anion transporting polypeptides influence hepatic enhancement in gadoxetic acid-enhanced MRI.

Patients & methods: We analyzed the genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, SLCO1B3 334T>G and NR1H4 -1G>T and calculated the mean quantitative liver-spleen contrast ratio, as an index of liver parenchymal enhancement, in 226 patients with liver disease.

Results: Multiple linear regression analysis using the mean quantitative liver-spleen contrast ratio as the dependent variable revealed that not only Child-Pugh score, but also SLCO1B1*1b haplotype (β = 0.12; p = 0.04), were significant predictors of liver parenchymal enhancement. In addition, SLCO1B3 334T>G (β = -0.18; p = 0.03) was a significant predictor when the data were analyzed in a subgroup of 117 patients, excluding the carriers of NR1H4 -1G>T, who reportedly exhibit reduced transcriptional activity of SLCO1B3.

Conclusion: These genetic variants, as well as hepatic function, may contribute to individual differences in hepatic enhancement with gadoxetic acid.

MeSH terms

  • Aged
  • Female
  • Gadolinium DTPA / metabolism*
  • Haplotypes
  • Humans
  • Image Enhancement / methods
  • Liver / metabolism*
  • Liver Diseases / genetics*
  • Liver-Specific Organic Anion Transporter 1
  • Magnetic Resonance Imaging / methods*
  • Male
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Polymorphism, Genetic / genetics*
  • Solute Carrier Organic Anion Transporter Family Member 1B3

Substances

  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • gadolinium ethoxybenzyl DTPA
  • Gadolinium DTPA