دورية أكاديمية
Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
| العنوان: | Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease |
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| المؤلفون: | 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., Marasa M., Shang N., Cohen D. J., Crew R. J., Morello W., Canetta P., Radhakrishnan J., Martino J., Liu Q., Chung W. K., Espinoza A., Luo Y., Wei W. -Q., Feng Q., Weng C., Fang Y., Kullo I. J., Naderian M., Limdi N., Irvin M. R., Tiwari H., Mohan S., Rao M., Dube G. K., Chaudhary N. S., Gutierrez O. M., Judd S. E., Cushman M., Lange L. A., Lange E. M., Bivona D. L., Verbitsky M., Winkler C. A., Kopp J. B., Santoriello D., Batal I., Pinheiro S. V. B., Oliveira E. A., Simoes e Silva A. C., Pisani I., Fiaccadori E., Lin F., Gesualdo L., Amoroso A., Ghiggeri G. M., D'Agati V. D., Magistroni R., Kenny E. E., Loos R. J. F., Montini G., Hildebrandt F., Paul D. S., Petrovski S., Goldstein D. B., Kretzler M., Gbadegesin R., Gharavi A. G., Kiryluk K., Sampson M. G., Pollak M. R., Sanna-Cherchi S. |
| المساهمون: | 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., Marasa, M., Shang, N., Cohen, D. J., Crew, R. J., Morello, W., Canetta, P., Radhakrishnan, J., Martino, J., Liu, Q., Chung, W. K., Espinoza, A., Luo, Y., Wei, W. -Q., Feng, Q., Weng, C., Fang, Y., Kullo, I. J., Naderian, M., Limdi, N., Irvin, M. R., Tiwari, H., Mohan, S., Rao, M., Dube, G. K., Chaudhary, N. S., Gutierrez, O. M., Judd, S. E., Cushman, M., Lange, L. A., Lange, E. M., Bivona, D. L., Verbitsky, M., Winkler, C. A., Kopp, J. B., Santoriello, D., Batal, I., Pinheiro, S. V. B., Oliveira, E. A., Simoes e Silva, A. C., Pisani, I., Fiaccadori, E., Lin, F., Gesualdo, L., Amoroso, A., Ghiggeri, G. M., D'Agati, V. D., Magistroni, R., Kenny, E. E., Loos, R. J. F., Montini, G., Hildebrandt, F., Paul, D. S., Petrovski, S., Goldstein, D. B., Kretzler, M., Gbadegesin, R., Gharavi, A. G., Kiryluk, K., Sampson, M. G., Pollak, M. R., Sanna-Cherchi, S. |
| سنة النشر: | 2023 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/38036523; volume:14; issue:1; firstpage:7836; lastpage:7844; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/11380/1329087Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85178413239 |
| DOI: | 10.1038/s41467-023-43020-9 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-43020-9Test https://hdl.handle.net/11380/1329087Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.46DE92F7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-43020-9 |
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