An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients

dc.contributor.authorThomford, Nicholas E.
dc.contributor.authorAdu, Faustina
dc.contributor.authorGavor-Kwashi, Cyril
dc.contributor.authorNyarko, Samuel B.
dc.contributor.authorNsiah, Paul
dc.contributor.authorEphraim, Richard D.
dc.contributor.authorAdjei, George
dc.contributor.authorAnyanful, Akwasi
dc.date.accessioned2023-08-08T13:31:02Z
dc.date.available2023-08-08T13:31:02Z
dc.date.issued2023-07-27
dc.date.updated2023-07-30T03:15:15Z
dc.description.abstractAbstract Background Organic anion transporters and efflux transporters are involved in the metabolism of drugs such as tenofovir disoproxil fumarate (TDF). Given the important role of organic anions and efflux transporters in drug disposition, genetic variations lead to interindividual differences in drug response. Variations in the SLC and ABC transporters have been associated with drug-induced renal dysfunction. Looking at the prevalence of HBV infection in our population and the use of drugs such as TDF in managing this condition, this study aimed to undertake an exploratory analysis of genetic variation in renal transporters SLC22A6, SLC22A8, ABCC10 and ABCC4 in a Ghanaian HBV infected cohort. Methods We genotyped 160 HBV infected patients for SNPs in SLC22A6 (rs12293966, rs4149170, rs6591722, rs955434), SLC22A8 (rs11568487), ABCC10 (rs700008, rs831311) and ABCC4 (rs9282570) genes. Clinicodemographic data was taken, and glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Genotyping was undertaken using Iplex gold SNP genotyping protocol on the Agena MassARRAY® system. Statistical analysis was undertaken using packages in Stata SE (v17) and GraphPad prism. Hardy–Weinberg equilibrium, haplotype inference, and linkage disequilibrium (LD) were evaluated using web-based tools LDlink and Shesis. Results The average eGFR was 79.78 ± 33.08 mL/min/1.73 m2 with 31% classified as stage 1 with normal or high GFR (eGFR > 90 mL/min/1.73 m2) and 45% with stage 2 CKD (> 60–89.99 mL/min/1.73 m2). All variants were in HWE except rs4149170, rs9282570 and rs700008 where p < 0.05. Strong LD was observed in the variants rs6591722, rs4149170, rs12293966, rs955434 and rs11568487. There was significant association between rs12293966 and eGFR stage under crude dominant inheritance model (OR 0.27, 95% CI 0.08–0.81; p = 0.019). Under crude model (OR 0.21, 95% CI 0.07–0.66; p = 0.008), adjusted model 1 (OR 76, 95% CI 0.39–7.89; p = 0.014) and adjusted model 2 (OR 0.30, 95% CI 0.12–0.78; p = 0.013) there was significant association observed between rs12293966 and eGFR stage in a codominant inheritance. Conclusion The associations observed in this study point to the need for further evaluation with the population of HBV patients on TDF treatment in addition to other factors that would lead to unfavorable outcomes. This exploratory finding may require confirmation in a larger cohort with proper phenotyping to investigate the exact pharmacogenetic mechanisms.en_US
dc.identifier.apacitationThomford, Nicholas E., Adu, F., Gavor-Kwashi, C., Nyarko, Samuel B., Nsiah, P., Ephraim, Richard D., ... Anyanful, A. (2023). An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients. <i>Egyptian Journal of Medical Human Genetics</i>, 24(1), 50. http://hdl.handle.net/11427/38215en_ZA
dc.identifier.chicagocitationThomford, Nicholas E., Faustina Adu, Cyril Gavor-Kwashi, Samuel B. Nyarko, Paul Nsiah, Richard D. Ephraim, George Adjei, and Akwasi Anyanful "An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients." <i>Egyptian Journal of Medical Human Genetics</i> 24, 1. (2023): 50. http://hdl.handle.net/11427/38215en_ZA
dc.identifier.citationThomford, Nicholas E., Adu, F., Gavor-Kwashi, C., Nyarko, Samuel B., Nsiah, P., Ephraim, Richard D., Adjei, G. & Anyanful, A. et al. 2023. An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients. <i>Egyptian Journal of Medical Human Genetics.</i> 24(1):50. http://hdl.handle.net/11427/38215en_ZA
dc.identifier.ris TY - Journal Article AU - Thomford, Nicholas E. AU - Adu, Faustina AU - Gavor-Kwashi, Cyril AU - Nyarko, Samuel B. AU - Nsiah, Paul AU - Ephraim, Richard D. AU - Adjei, George AU - Anyanful, Akwasi AB - Abstract Background Organic anion transporters and efflux transporters are involved in the metabolism of drugs such as tenofovir disoproxil fumarate (TDF). Given the important role of organic anions and efflux transporters in drug disposition, genetic variations lead to interindividual differences in drug response. Variations in the SLC and ABC transporters have been associated with drug-induced renal dysfunction. Looking at the prevalence of HBV infection in our population and the use of drugs such as TDF in managing this condition, this study aimed to undertake an exploratory analysis of genetic variation in renal transporters SLC22A6, SLC22A8, ABCC10 and ABCC4 in a Ghanaian HBV infected cohort. Methods We genotyped 160 HBV infected patients for SNPs in SLC22A6 (rs12293966, rs4149170, rs6591722, rs955434), SLC22A8 (rs11568487), ABCC10 (rs700008, rs831311) and ABCC4 (rs9282570) genes. Clinicodemographic data was taken, and glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Genotyping was undertaken using Iplex gold SNP genotyping protocol on the Agena MassARRAY® system. Statistical analysis was undertaken using packages in Stata SE (v17) and GraphPad prism. Hardy–Weinberg equilibrium, haplotype inference, and linkage disequilibrium (LD) were evaluated using web-based tools LDlink and Shesis. Results The average eGFR was 79.78 ± 33.08 mL/min/1.73 m2 with 31% classified as stage 1 with normal or high GFR (eGFR > 90 mL/min/1.73 m2) and 45% with stage 2 CKD (> 60–89.99 mL/min/1.73 m2). All variants were in HWE except rs4149170, rs9282570 and rs700008 where p < 0.05. Strong LD was observed in the variants rs6591722, rs4149170, rs12293966, rs955434 and rs11568487. There was significant association between rs12293966 and eGFR stage under crude dominant inheritance model (OR 0.27, 95% CI 0.08–0.81; p = 0.019). Under crude model (OR 0.21, 95% CI 0.07–0.66; p = 0.008), adjusted model 1 (OR 76, 95% CI 0.39–7.89; p = 0.014) and adjusted model 2 (OR 0.30, 95% CI 0.12–0.78; p = 0.013) there was significant association observed between rs12293966 and eGFR stage in a codominant inheritance. Conclusion The associations observed in this study point to the need for further evaluation with the population of HBV patients on TDF treatment in addition to other factors that would lead to unfavorable outcomes. This exploratory finding may require confirmation in a larger cohort with proper phenotyping to investigate the exact pharmacogenetic mechanisms. DA - 2023-07-27 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Egyptian Journal of Medical Human Genetics KW - Tenofovir KW - SLC22A6 KW - HBV KW - Pharmacogenetics KW - eGFR KW - Renal impairment KW - Transporters LK - https://open.uct.ac.za PY - 2023 T1 - An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients TI - An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients UR - http://hdl.handle.net/11427/38215 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s43042-023-00428-8
dc.identifier.urihttp://hdl.handle.net/11427/38215
dc.identifier.vancouvercitationThomford Nicholas E, Adu F, Gavor-Kwashi C, Nyarko Samuel B, Nsiah P, Ephraim Richard D, et al. An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients. Egyptian Journal of Medical Human Genetics. 2023;24(1):50. http://hdl.handle.net/11427/38215.en_ZA
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceEgyptian Journal of Medical Human Geneticsen_US
dc.source.journalissue1en_US
dc.source.journalvolume24en_US
dc.source.pagination50en_US
dc.source.urihttps://jmhg.springeropen.com/
dc.subjectTenofoviren_US
dc.subjectSLC22A6en_US
dc.subjectHBVen_US
dc.subjectPharmacogeneticsen_US
dc.subjecteGFRen_US
dc.subjectRenal impairmenten_US
dc.subjectTransportersen_US
dc.titleAn exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patientsen_US
dc.typeJournal Articleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
43042_2023_Article_428.pdf
Size:
1.22 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description:
Collections