title: 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.
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Meiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ran
authors.initials: R
authors.lastname: Nakashima
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imura
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yoshifuji
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Yukawa
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000328:Adult; D000368:Aged; D003240:Connective Tissue Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus