Pharmacogenetics of Immunosuppressant Polymorphism of CYP3A5 in Renal Transplant Recipients

Investigation of CYP 3A5 and ABCB1 gene polymorphisms in the long-term following renal transplantation: Effects on tacrolimus exposure and kidney function

“…The results of the present study showed that the CYP 3A5 * 1 allele was present in 7% of the tested population (which comprised only Caucasian individuals), which was consistent with previous findings in Caucasians of ~5-15% (17). The frequency of this allele varies among other ethnic groups, and has been reported to be 45-73% in African-Americans, 15% in Japanese, 27-35% in Chinese, 30% in Koreans, 25% in Mexicans, 27% in Moroccans and 26% in Brazilians (9,(18)(19)(20).…”

“…Previous studies did not show a difference in allele frequency between renal transplant patients and healthy volunteers, but revealed that the CYP 3A5 * 1 allele frequency is largely dependent on ethnic origin (5,17). The results of the present study showed that the CYP 3A5 * 1 allele was present in 7% of the tested population (which comprised only Caucasian individuals), which was consistent with previous findings in Caucasians of ~5-15% (17).…”

Identification of CYP3A5 and CYP2B6 Polymorphisms in Porphyria Cutanea Tarda Associated to Human Immunodeficiency Virus

“…We have shown that the allelic frequency of CYP3A5*3 in our population was similar to that reported for other Caucasian populations (91.7%) [31]. Larriba et al [32] in an Argentinean group of renal transplanted subjects found that 89% of the individuals analyzed were homozygotes and 11% were heterozygotes for the allele CYP3A5*3. In this work, the frequency was different from studies of African American, Hispanic [33] and Japanese patients [33].…”

Review article: The pharmacokinetics and pharmacodynamics of drugs used in inflammatory bowel disease treatment

“…Concerning CYP3A5, only individuals with the wild-type CYP3A5*1 allele display normal enzymatic activity (25-40 % higher clearance) [182,202]. It has been shown that these patients require higher doses (50 to 70 %) to target trough levels of tacrolimus in renal transplant recipients [203,204].…”

“…The CYP3A5*3 allele codes for a nonfunctional protein resulting in poor drug metabolism in the homozygous The same indications apply as for thiopurine therapy, but at present, MTX is generally reserved for treatment of active or relapsing CD in those refractory to or intolerant of thiopurines or anti-TNF agents *3/*3 patient (i.e. poor metabolizers) [202]. Accordingly, the *1/*3 heterozygous population is an intermediate metabolizer of CYP3A5 substrates of tacrolimus [202].…”