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Significant association between CYP3A5 polymorphism and blood concentration of tacrolimus in patients with connective tissue diseases.

Abstract
Although the association between CYP3A5 polymorphism and blood concentration of tacrolimus (TAC) in patients with solid organ transplantation was established, whether the association is also true in patients with connective tissue disease (CTD) who usually receive small amount of TAC is uncertain. Here, we performed a quantitative linear regression analysis to address the association between CYP3A5 and blood TAC concentration in patients with CTD. A total of 72 patients with CTD were recruited in the current study and genotyped for rs776746 in CYP3A5, which showed strong association with TAC concentration in patients with solid organ transplantation. The blood trough concentration of TAC after taking 3 mg per day was retrospectively obtained for each patient. As a result, allele A of rs776746 showed a significant association with a decreasing blood concentration of TAC (P=0.0038). Those who are carrying at least one copy of the A allele displayed decreased mean concentration of TAC by 31.0% compared with subjects with GG genotype. Rs776746 is associated with concentrations of TAC in patients with CTD.
AuthorsKosuke Tanaka, Chikashi Terao, Koichiro Ohmura, Meiko Takahashi, Ran Nakashima, Yoshitaka Imura, Hajime Yoshifuji, Naoichiro Yukawa, Takashi Usui, Takao Fujii, Tsuneyo Mimori, Fumihiko Matsuda
JournalJournal of human genetics (J Hum Genet) Vol. 59 Issue 2 Pg. 107-9 (Feb 2014) ISSN: 1435-232X [Electronic] England
PMID24352002 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunosuppressive Agents
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus
Topics
  • Adult
  • Aged
  • Connective Tissue Diseases (drug therapy, enzymology, genetics)
  • Cytochrome P-450 CYP3A (genetics, metabolism)
  • Female
  • Humans
  • Immunosuppressive Agents (administration & dosage, pharmacokinetics)
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Tacrolimus (administration & dosage, pharmacokinetics)

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