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Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease. / Gupta, Yask; Friedman, David J.; McNulty, Michelle T.; Khan, Atlas; Lane, Brandon; Wang, Chen; Ke, Juntao; Jin, Gina; Wooden, Benjamin; Knob, Andrea L.; Lim, Tze Y.; Appel, Gerald B.; Huggins, Kinsie; Liu, Lili; Mitrotti, Adele; Stangl, Megan C.; Bomback, Andrew; Westland, Rik; Bodria, Monica; Marasa, Maddalena; Shang, Ning; Cohen, David J.; Crew, Russell J.; Morello, William; Canetta, Pietro; Radhakrishnan, Jai; Martino, Jeremiah; Liu, Qingxue; Chung, Wendy K.; Espinoza, Angelica; Luo, Yuan; Wei, Wei-Qi; Feng, Qiping; Weng, Chunhua; Fang, Yilu; Kullo, Iftikhar J.; Naderian, Mohammadreza; Limdi, Nita; Irvin, Marguerite R.; Tiwari, Hemant; Mohan, Sumit; Rao, Maya; Dube, Geoffrey K.; Chaudhary, Ninad S.; Gutiérrez, Orlando M.; Judd, Suzanne E.; Cushman, Mary; Lange, Leslie A.; Lange, Ethan M.; Bivona, Daniel L.; Verbitsky, Miguel; Winkler, Cheryl A.; Kopp, Jeffrey B.; Santoriello, Dominick; Batal, Ibrahim; Pinheiro, Sérgio Veloso Brant; Oliveira, Eduardo Araújo; Simoes e Silva, Ana Cristina; Pisani, Isabella; Fiaccadori, Enrico; Lin, Fangming; Gesualdo, Loreto; Amoroso, Antonio; Ghiggeri, Gian Marco; D’Agati, Vivette D.; Magistroni, Riccardo; Kenny, Eimear E.; Loos, Ruth J.F.; Montini, Giovanni; Hildebrandt, Friedhelm; Paul, Dirk S.; Petrovski, Slavé; Goldstein, David B.; Kretzler, Matthias; Gbadegesin, Rasheed; Gharavi, Ali G.; Kiryluk, Krzysztof; Sampson, Matthew G.; Pollak, Martin R.; Sanna-Cherchi, Simone.
In:
Nature Communications, Vol. 14, 7836, 2023.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Gupta, Y, Friedman, DJ, McNulty, MT, Khan, A, Lane, B, Wang, C, Ke, J, Jin, G, Wooden, B, Knob, AL, Lim, TY, Appel, GB, Huggins, K, Liu, L, Mitrotti, A, Stangl, MC, Bomback, A, Westland, R, Bodria, M, Marasa, M, Shang, N, Cohen, DJ, Crew, RJ, Morello, W, Canetta, P, Radhakrishnan, J, Martino, J, Liu, Q, Chung, WK, Espinoza, A, Luo, Y, Wei, W-Q, Feng, Q, Weng, C, Fang, Y, Kullo, IJ, Naderian, M, Limdi, N, Irvin, MR, Tiwari, H, Mohan, S, Rao, M, Dube, GK, Chaudhary, NS, Gutiérrez, OM, Judd, SE, Cushman, M, Lange, LA, Lange, EM, Bivona, DL, Verbitsky, M, Winkler, CA, Kopp, JB, Santoriello, D, Batal, I, Pinheiro, SVB, Oliveira, EA, Simoes e Silva, AC, Pisani, I, Fiaccadori, E, Lin, F, Gesualdo, L, Amoroso, A, Ghiggeri, GM, D’Agati, VD, Magistroni, R, Kenny, EE
, Loos, RJF, Montini, G, Hildebrandt, F, Paul, DS, Petrovski, S, Goldstein, DB, Kretzler, M, Gbadegesin, R, Gharavi, AG, Kiryluk, K, Sampson, MG, Pollak, MR & Sanna-Cherchi, S 2023, '
Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease',
Nature Communications, vol. 14, 7836.
https://doi.org/10.1038/s41467-023-43020-9APA
Gupta, Y., Friedman, D. J., McNulty, M. T., Khan, A., Lane, B., Wang, C., Ke, J., Jin, G., Wooden, B., Knob, A. L., Lim, T. Y., Appel, G. B., Huggins, K., Liu, L., Mitrotti, A., Stangl, M. C., Bomback, A., Westland, R., Bodria, M., ... Sanna-Cherchi, S. (2023).
Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.
Nature Communications,
14, [7836].
https://doi.org/10.1038/s41467-023-43020-9Vancouver
Gupta Y, Friedman DJ, McNulty MT, Khan A, Lane B, Wang C et al.
Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.
Nature Communications. 2023;14. 7836.
https://doi.org/10.1038/s41467-023-43020-9Author
Gupta, Yask ; Friedman, David J. ; McNulty, Michelle T. ; Khan, Atlas ; Lane, Brandon ; Wang, Chen ; Ke, Juntao ; Jin, Gina ; Wooden, Benjamin ; Knob, Andrea L. ; Lim, Tze Y. ; Appel, Gerald B. ; Huggins, Kinsie ; Liu, Lili ; Mitrotti, Adele ; Stangl, Megan C. ; Bomback, Andrew ; Westland, Rik ; Bodria, Monica ; Marasa, Maddalena ; Shang, Ning ; Cohen, David J. ; Crew, Russell J. ; Morello, William ; Canetta, Pietro ; Radhakrishnan, Jai ; Martino, Jeremiah ; Liu, Qingxue ; Chung, Wendy K. ; Espinoza, Angelica ; Luo, Yuan ; Wei, Wei-Qi ; Feng, Qiping ; Weng, Chunhua ; Fang, Yilu ; Kullo, Iftikhar J. ; Naderian, Mohammadreza ; Limdi, Nita ; Irvin, Marguerite R. ; Tiwari, Hemant ; Mohan, Sumit ; Rao, Maya ; Dube, Geoffrey K. ; Chaudhary, Ninad S. ; Gutiérrez, Orlando M. ; Judd, Suzanne E. ; Cushman, Mary ; Lange, Leslie A. ; Lange, Ethan M. ; Bivona, Daniel L. ; Verbitsky, Miguel ; Winkler, Cheryl A. ; Kopp, Jeffrey B. ; Santoriello, Dominick ; Batal, Ibrahim ; Pinheiro, Sérgio Veloso Brant ; Oliveira, Eduardo Araújo ; Simoes e Silva, Ana Cristina ; Pisani, Isabella ; Fiaccadori, Enrico ; Lin, Fangming ; Gesualdo, Loreto ; Amoroso, Antonio ; Ghiggeri, Gian Marco ; D’Agati, Vivette D. ; Magistroni, Riccardo ; Kenny, Eimear E. ; Loos, Ruth J.F. ; Montini, Giovanni ; Hildebrandt, Friedhelm ; Paul, Dirk S. ; Petrovski, Slavé ; Goldstein, David B. ; Kretzler, Matthias ; Gbadegesin, Rasheed ; Gharavi, Ali G. ; Kiryluk, Krzysztof ; Sampson, Matthew G. ; Pollak, Martin R. ; Sanna-Cherchi, Simone. / Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease. In: Nature Communications. 2023 ; Vol. 14.
Bibtex
@article{5fbee1f475ca46678c7b72d29c17016b,
title = "Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease",
abstract = "African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.",
author = "Yask Gupta and Friedman, {David J.} and McNulty, {Michelle T.} and Atlas Khan and Brandon Lane and Chen Wang and Juntao Ke and Gina Jin and Benjamin Wooden and Knob, {Andrea L.} and Lim, {Tze Y.} and Appel, {Gerald B.} and Kinsie Huggins and Lili Liu and Adele Mitrotti and Stangl, {Megan C.} and Andrew Bomback and Rik Westland and Monica Bodria and Maddalena Marasa and Ning Shang and Cohen, {David J.} and Crew, {Russell J.} and William Morello and Pietro Canetta and Jai Radhakrishnan and Jeremiah Martino and Qingxue Liu and Chung, {Wendy K.} and Angelica Espinoza and Yuan Luo and Wei-Qi Wei and Qiping Feng and Chunhua Weng and Yilu Fang and Kullo, {Iftikhar J.} and Mohammadreza Naderian and Nita Limdi and Irvin, {Marguerite R.} and Hemant Tiwari and Sumit Mohan and Maya Rao and Dube, {Geoffrey K.} and Chaudhary, {Ninad S.} and Guti{\'e}rrez, {Orlando M.} and Judd, {Suzanne E.} and Mary Cushman and Lange, {Leslie A.} and Lange, {Ethan M.} and Bivona, {Daniel L.} and Miguel Verbitsky and Winkler, {Cheryl A.} and Kopp, {Jeffrey B.} and Dominick Santoriello and Ibrahim Batal and Pinheiro, {S{\'e}rgio Veloso Brant} and Oliveira, {Eduardo Ara{\'u}jo} and {Simoes e Silva}, {Ana Cristina} and Isabella Pisani and Enrico Fiaccadori and Fangming Lin and Loreto Gesualdo and Antonio Amoroso and Ghiggeri, {Gian Marco} and D{\textquoteright}Agati, {Vivette D.} and Riccardo Magistroni and Kenny, {Eimear E.} and Loos, {Ruth J.F.} and Giovanni Montini and Friedhelm Hildebrandt and Paul, {Dirk S.} and Slav{\'e} Petrovski and Goldstein, {David B.} and Matthias Kretzler and Rasheed Gbadegesin and Gharavi, {Ali G.} and Krzysztof Kiryluk and Sampson, {Matthew G.} and Pollak, {Martin R.} and Simone Sanna-Cherchi",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41467-023-43020-9",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
}
RIS
TY - JOUR
T1 - Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
AU - Gupta, Yask
AU - Friedman, David J.
AU - McNulty, Michelle T.
AU - Khan, Atlas
AU - Lane, Brandon
AU - Wang, Chen
AU - Ke, Juntao
AU - Jin, Gina
AU - Wooden, Benjamin
AU - Knob, Andrea L.
AU - Lim, Tze Y.
AU - Appel, Gerald B.
AU - Huggins, Kinsie
AU - Liu, Lili
AU - Mitrotti, Adele
AU - Stangl, Megan C.
AU - Bomback, Andrew
AU - Westland, Rik
AU - Bodria, Monica
AU - Marasa, Maddalena
AU - Shang, Ning
AU - Cohen, David J.
AU - Crew, Russell J.
AU - Morello, William
AU - Canetta, Pietro
AU - Radhakrishnan, Jai
AU - Martino, Jeremiah
AU - Liu, Qingxue
AU - Chung, Wendy K.
AU - Espinoza, Angelica
AU - Luo, Yuan
AU - Wei, Wei-Qi
AU - Feng, Qiping
AU - Weng, Chunhua
AU - Fang, Yilu
AU - Kullo, Iftikhar J.
AU - Naderian, Mohammadreza
AU - Limdi, Nita
AU - Irvin, Marguerite R.
AU - Tiwari, Hemant
AU - Mohan, Sumit
AU - Rao, Maya
AU - Dube, Geoffrey K.
AU - Chaudhary, Ninad S.
AU - Gutiérrez, Orlando M.
AU - Judd, Suzanne E.
AU - Cushman, Mary
AU - Lange, Leslie A.
AU - Lange, Ethan M.
AU - Bivona, Daniel L.
AU - Verbitsky, Miguel
AU - Winkler, Cheryl A.
AU - Kopp, Jeffrey B.
AU - Santoriello, Dominick
AU - Batal, Ibrahim
AU - Pinheiro, Sérgio Veloso Brant
AU - Oliveira, Eduardo Araújo
AU - Simoes e Silva, Ana Cristina
AU - Pisani, Isabella
AU - Fiaccadori, Enrico
AU - Lin, Fangming
AU - Gesualdo, Loreto
AU - Amoroso, Antonio
AU - Ghiggeri, Gian Marco
AU - D’Agati, Vivette D.
AU - Magistroni, Riccardo
AU - Kenny, Eimear E.
AU - Loos, Ruth J.F.
AU - Montini, Giovanni
AU - Hildebrandt, Friedhelm
AU - Paul, Dirk S.
AU - Petrovski, Slavé
AU - Goldstein, David B.
AU - Kretzler, Matthias
AU - Gbadegesin, Rasheed
AU - Gharavi, Ali G.
AU - Kiryluk, Krzysztof
AU - Sampson, Matthew G.
AU - Pollak, Martin R.
AU - Sanna-Cherchi, Simone
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
AB - African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
U2 - 10.1038/s41467-023-43020-9
DO - 10.1038/s41467-023-43020-9
M3 - Journal article
C2 - 38036523
AN - SCOPUS:85178413239
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7836
ER -
