Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients
This study aimed to systematically investigate trans-eQTLs of CYP3A4 and CYP3A5 affecting tacrolimus trough blood concentrations in Chinese renal transplant patients. We used Plink v1.90 to perform data quality control and linear regression analysis on GTEx v8 data. SNPs with p-value < 0.05 were...
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Elsevier
2022
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oai:doaj.org-article:cdbe852b1c434da889ba57205a394fe62021-11-14T04:30:31ZTrans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients0753-332210.1016/j.biopha.2021.112407https://doaj.org/article/cdbe852b1c434da889ba57205a394fe62022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221011938https://doaj.org/toc/0753-3322This study aimed to systematically investigate trans-eQTLs of CYP3A4 and CYP3A5 affecting tacrolimus trough blood concentrations in Chinese renal transplant patients. We used Plink v1.90 to perform data quality control and linear regression analysis on GTEx v8 data. SNPs with p-value < 0.05 were selected and the GTEx eQTL Calculator was used to further prioritize the eQTLs of CYP3A4 and CYP3A5 in the liver and small intestine. The eQTLs with a p-value < 5 × 10−5 and MAF≥ 0.05 in the CHB population were selected as candidate eQTLs. The genotyping of candidate eQTLs was performed using high-resolution melting (HRM) assays and Sanger DNA sequencing. This study included 845 Chinese renal transplant patients who received tacrolimus as an immunosuppressive agent. Association between 103 candidate eQTLs and log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in this cohort was conducted using the SNPassoc package of R software. In the end, a total of 75,632 liver eQTLs of CYP3A4, 69,558 liver eQTLs of CYP3A5, 48,596 small intestine eQTLs of CYP3A4 and 28,616 small intestine eQTLs of CYP3A5 were obtained using the GTEx v8 eQTL Calculator. Of the 103 candidate eQTLs, rs75727207, rs181294422 and rs28522676 were significantly associated with tacrolimus log(C0/D) in different genetic models. We discovered a substantial number of novel eQTLs of CYP3A4 and CYP3A5 in liver and small intestine, also found that rs75727207, rs181294422 and rs28522676 may affect tacrolimus trough blood concentrations in Chinese renal transplant patients.Huijie LuHaixia JiangSiyao YangChengcheng LiChuanjiang LiRuifan ShaoPai ZhangDaoyi WangZhiwei LiuHuana QiYinuan CaiWenbin XuXiaojie BaoHailan WangLiang LiElsevierarticleCYP3A5CYP3A4TacrolimusTrans-eQTLGTExTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112407- (2022) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
CYP3A5 CYP3A4 Tacrolimus Trans-eQTL GTEx Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
CYP3A5 CYP3A4 Tacrolimus Trans-eQTL GTEx Therapeutics. Pharmacology RM1-950 Huijie Lu Haixia Jiang Siyao Yang Chengcheng Li Chuanjiang Li Ruifan Shao Pai Zhang Daoyi Wang Zhiwei Liu Huana Qi Yinuan Cai Wenbin Xu Xiaojie Bao Hailan Wang Liang Li Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| description |
This study aimed to systematically investigate trans-eQTLs of CYP3A4 and CYP3A5 affecting tacrolimus trough blood concentrations in Chinese renal transplant patients. We used Plink v1.90 to perform data quality control and linear regression analysis on GTEx v8 data. SNPs with p-value < 0.05 were selected and the GTEx eQTL Calculator was used to further prioritize the eQTLs of CYP3A4 and CYP3A5 in the liver and small intestine. The eQTLs with a p-value < 5 × 10−5 and MAF≥ 0.05 in the CHB population were selected as candidate eQTLs. The genotyping of candidate eQTLs was performed using high-resolution melting (HRM) assays and Sanger DNA sequencing. This study included 845 Chinese renal transplant patients who received tacrolimus as an immunosuppressive agent. Association between 103 candidate eQTLs and log-transformed tacrolimus concentration/dose ratio (log (C0/D)) in this cohort was conducted using the SNPassoc package of R software. In the end, a total of 75,632 liver eQTLs of CYP3A4, 69,558 liver eQTLs of CYP3A5, 48,596 small intestine eQTLs of CYP3A4 and 28,616 small intestine eQTLs of CYP3A5 were obtained using the GTEx v8 eQTL Calculator. Of the 103 candidate eQTLs, rs75727207, rs181294422 and rs28522676 were significantly associated with tacrolimus log(C0/D) in different genetic models. We discovered a substantial number of novel eQTLs of CYP3A4 and CYP3A5 in liver and small intestine, also found that rs75727207, rs181294422 and rs28522676 may affect tacrolimus trough blood concentrations in Chinese renal transplant patients. |
| format |
article |
| author |
Huijie Lu Haixia Jiang Siyao Yang Chengcheng Li Chuanjiang Li Ruifan Shao Pai Zhang Daoyi Wang Zhiwei Liu Huana Qi Yinuan Cai Wenbin Xu Xiaojie Bao Hailan Wang Liang Li |
| author_facet |
Huijie Lu Haixia Jiang Siyao Yang Chengcheng Li Chuanjiang Li Ruifan Shao Pai Zhang Daoyi Wang Zhiwei Liu Huana Qi Yinuan Cai Wenbin Xu Xiaojie Bao Hailan Wang Liang Li |
| author_sort |
Huijie Lu |
| title |
Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| title_short |
Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| title_full |
Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| title_fullStr |
Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| title_full_unstemmed |
Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients |
| title_sort |
trans-eqtls of the cyp3a4 and cyp3a5 associated with tacrolimus trough blood concentration in chinese renal transplant patients |
| publisher |
Elsevier |
| publishDate |
2022 |
| url |
https://doaj.org/article/cdbe852b1c434da889ba57205a394fe6 |
| work_keys_str_mv |
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