Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans. Mateza, S., Bradford, Y., Maartens, G., Sokhela, S., Chandiwana, N. C, Venter, W. D F, Post, F. A, Ritchie, M. D, Haas, D. W, & Sinxadi, P. Pharmacogenetics and Genomics, 33(5):91–100, 2023. ![Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper abstract bibtex Objective Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans. Methods Genetic sub-study of adults was randomized to initiate TAF or TDF together with dolutegravir and emtricitabine. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine $β$2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations. Results 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7). Conclusion Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.
@article{Mateza2023,
abstract = {Objective Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans. Methods Genetic sub-study of adults was randomized to initiate TAF or TDF together with dolutegravir and emtricitabine. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine $\beta$2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations. Results 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7). Conclusion Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.},
author = {Mateza, Somila and Bradford, Yuki and Maartens, Gary and Sokhela, Simiso and Chandiwana, Nomathemba C and Venter, Willem D F and Post, Frank A and Ritchie, Marylyn D and Haas, David W and Sinxadi, Phumla},
issn = {1744-6872},
journal = {Pharmacogenetics and Genomics},
keywords = {HIV,OA,fund{\_}ack,original,pharmacogenetics,renal toxicity,tenofovir alafenamide fumarate,tenofovir disoproxil fumarate},
mendeley-tags = {OA,fund{\_}ack,original},
number = {5},
pages = {91--100},
pmid = {37099271},
title = {{Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans}},
url = {https://journals.lww.com/jpharmacogenetics/Fulltext/9900/Pharmacogenetics{\_}of{\_}tenofovir{\_}renal{\_}toxicity{\_}in.27.aspx},
volume = {33},
year = {2023}
}
Downloads: 0
{"_id":"kmKgbbSwNjchwCnJ6","bibbaseid":"mateza-bradford-maartens-sokhela-chandiwana-venter-post-ritchie-etal-pharmacogeneticsoftenofovirrenaltoxicityinhivpositivesouthernafricans-2023","author_short":["Mateza, S.","Bradford, Y.","Maartens, G.","Sokhela, S.","Chandiwana, N. C","Venter, W. D F","Post, F. A","Ritchie, M. D","Haas, D. W","Sinxadi, P."],"bibdata":{"bibtype":"article","type":"article","abstract":"Objective Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans. Methods Genetic sub-study of adults was randomized to initiate TAF or TDF together with dolutegravir and emtricitabine. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine $β$2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations. Results 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7). Conclusion Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.","author":[{"propositions":[],"lastnames":["Mateza"],"firstnames":["Somila"],"suffixes":[]},{"propositions":[],"lastnames":["Bradford"],"firstnames":["Yuki"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Sokhela"],"firstnames":["Simiso"],"suffixes":[]},{"propositions":[],"lastnames":["Chandiwana"],"firstnames":["Nomathemba","C"],"suffixes":[]},{"propositions":[],"lastnames":["Venter"],"firstnames":["Willem","D","F"],"suffixes":[]},{"propositions":[],"lastnames":["Post"],"firstnames":["Frank","A"],"suffixes":[]},{"propositions":[],"lastnames":["Ritchie"],"firstnames":["Marylyn","D"],"suffixes":[]},{"propositions":[],"lastnames":["Haas"],"firstnames":["David","W"],"suffixes":[]},{"propositions":[],"lastnames":["Sinxadi"],"firstnames":["Phumla"],"suffixes":[]}],"issn":"1744-6872","journal":"Pharmacogenetics and Genomics","keywords":"HIV,OA,fund_ack,original,pharmacogenetics,renal toxicity,tenofovir alafenamide fumarate,tenofovir disoproxil fumarate","mendeley-tags":"OA,fund_ack,original","number":"5","pages":"91–100","pmid":"37099271","title":"Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans","url":"https://journals.lww.com/jpharmacogenetics/Fulltext/9900/Pharmacogenetics\\_of\\_tenofovir\\_renal\\_toxicity\\_in.27.aspx","volume":"33","year":"2023","bibtex":"@article{Mateza2023,\r\nabstract = {Objective Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans. Methods Genetic sub-study of adults was randomized to initiate TAF or TDF together with dolutegravir and emtricitabine. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine $\\beta$2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations. Results 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7). Conclusion Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.},\r\nauthor = {Mateza, Somila and Bradford, Yuki and Maartens, Gary and Sokhela, Simiso and Chandiwana, Nomathemba C and Venter, Willem D F and Post, Frank A and Ritchie, Marylyn D and Haas, David W and Sinxadi, Phumla},\r\nissn = {1744-6872},\r\njournal = {Pharmacogenetics and Genomics},\r\nkeywords = {HIV,OA,fund{\\_}ack,original,pharmacogenetics,renal toxicity,tenofovir alafenamide fumarate,tenofovir disoproxil fumarate},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nnumber = {5},\r\npages = {91--100},\r\npmid = {37099271},\r\ntitle = {{Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans}},\r\nurl = {https://journals.lww.com/jpharmacogenetics/Fulltext/9900/Pharmacogenetics{\\_}of{\\_}tenofovir{\\_}renal{\\_}toxicity{\\_}in.27.aspx},\r\nvolume = {33},\r\nyear = {2023}\r\n}\r\n","author_short":["Mateza, S.","Bradford, Y.","Maartens, G.","Sokhela, S.","Chandiwana, N. C","Venter, W. D F","Post, F. A","Ritchie, M. D","Haas, D. W","Sinxadi, P."],"key":"Mateza2023","id":"Mateza2023","bibbaseid":"mateza-bradford-maartens-sokhela-chandiwana-venter-post-ritchie-etal-pharmacogeneticsoftenofovirrenaltoxicityinhivpositivesouthernafricans-2023","role":"author","urls":{"Paper":"https://journals.lww.com/jpharmacogenetics/Fulltext/9900/Pharmacogenetics\\_of\\_tenofovir\\_renal\\_toxicity\\_in.27.aspx"},"keyword":["HIV","OA","fund_ack","original","pharmacogenetics","renal toxicity","tenofovir alafenamide fumarate","tenofovir disoproxil fumarate"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["hiv","oa","fund_ack","original","pharmacogenetics","renal toxicity","tenofovir alafenamide fumarate","tenofovir disoproxil fumarate"],"search_terms":["pharmacogenetics","tenofovir","renal","toxicity","hiv","positive","southern","africans","mateza","bradford","maartens","sokhela","chandiwana","venter","post","ritchie","haas","sinxadi"],"title":"Pharmacogenetics of tenofovir renal toxicity in HIV-positive Southern Africans","year":2023}