Background: Tacrolimus is a widely used immunosuppressant that prevents solid organ transplant rejection. The pharmacokinetics of Tacrolimus show considerable varia - bility. Interleukin-10 (IL-10), in the host's immune response after transplantation, contributes to the variable CYP3Adependent drug disposition of Tacrolimus. In the current study, we aim to evaluate the impact of single nucleotide polymorphisms (SNP) in the promoter region of IL-10 on Tacrolimus dose requirements and the Dose Adjusted Concentration (DAC) of Tacrolimus among kidney transplantation recipients.
Methods: Blood levels of Tacrolimus were measured using Microparticle Enzyme Immunoassay (MEIA) for six months post-transplantation. Genotyping analysis was utilized using specific Polymerase Chain Reaction (PCR) followed by sequencing methods for 98 Jordanian kidney transplant recipients.
Results: Genotyping frequencies of IL-10 (-592) were (CC/CA/AA: 38, 46.7, 15.2%); IL-10 (-819) were (CC/CT/TT: 40.4, 44.1, 15.1%); and IL-10 (-1082) were (AA/AG/GG: 42.6, 44.7, 12.8%). The impact of IL-10 (-1082) on Tacrolimus DAC was gender dependent. Men carrying at least one A allele had significantly lower DAC than men carrying GG genotyping only in the first month post-transplantation 88.2±32.1 vs. 117.5±22.5 ng/mL per mg/kg/day, p=0.04 .
Conclusions: Our current study showed that the interaction between gender and IL-10 -1082 affects Tacrolimus DAC in Jordanian kidney transplant recipients during the first month post-transplantation.
Uvod: Takrolimus je široko korišćen imunosupresiv koji sprečava odbacivanje presađenog čvrstog organa. Farmako-kinetika takrolimusa pokazuje značajnu varijabilnost interleukin-10 (IL-10), u imunološkom odgovoru domaćina nakon transplantacije, doprinosi promenljivoj dispoziciji leka zavisne od CIP3A kod takrolimusa. U ovoj studiji, cilj nam je da procenimo uticaj polimorfizama pojedinačnih nukleotida (SNP) u promotorskom regionu IL-10 na zahteve za dozom takrolimusa i koncentraciju prilagođenu dozi (DAC) takrolimusa među primaocima transplantacije bubrega.
Metode: Nivoi takrolimusa u krvi su mereni korišćenjem imunoeseja mikročestica enzima (MEIA) tokom šest meseci nakon transplantacije. Analiza genotipizacije je izvedena korišćenjem specifične lančane reakcije polimeraze (PCR) praćene metodama sekvenciranja za 98 jordanskih primalaca transplantiranih bubrega.
Rezultati: Učestalosti genotipizacije IL-10 (-592) su (CC/CA/AA: 38, 46,7, 15,2%); IL-10 (-819) su (CC/CT/TT: 40,4, 44,1, 15,1%); i IL-10 (-1082) su (AA/AG/GG: 42,6, 44,7, 12,8%). Uticaj IL-10 (-1082) na takrolimus DAC zavisio je od pola. Muškarci koji su nosili najmanje jedan alel A imali su značajno niži DAC od muškaraca koji su nosili genotipizaciju GG samo u prvom mesecu nakon trans plantacije 88,2±32,1 naspram 117,5±22,5 ng/mL po mg/kg/dan, p=0,04 .
Zaključak: Naša trenutna studija je pokazala da interakcija između pola i IL-10-1082 utiče na takrolimus DAC kod jordanskih primalaca transplantacije bubrega tokom prvog meseca nakon transplantacije.
Keywords: IL-10 genetic polymorphism; kidney transplantation; pharmacokinetics; tacrolimus.
2022 Bara'ah Khaleel, Al-Motassem Yousef, Mazhar Salim Al-Zoubi, Muhammad Al-Ulemat, Ahmad A. Masadeh, Ali Abuhaliema, Khalid M. Al-Batayneh, Bahaa Al-Trad, published by CEON/CEES.