MYH9 and APOL1 Gene Polymorphisms and the Risk of CKD in Patients with Lupus Nephritis from an Admixture Population

Carregando...
Imagem de Miniatura
Citações na Scopus
21
Tipo de produção
article
Data de publicação
2014
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Citação
PLOS ONE, v.9, n.3, article ID e87716, 8p, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
MYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95% CI 1.47-9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95% CI 1.2-3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.
Palavras-chave
Referências
  1. Alarcon GS, 1999, LUPUS, V8, P197, DOI 10.1191/096120399678847704
  2. AUSTIN HA, 1986, NEW ENGL J MED, V314, P614, DOI 10.1056/NEJM198603063141004
  3. Behar DM, 2010, HUM MOL GENET, V19, P1816, DOI 10.1093/hmg/ddq040
  4. Behar DM, 2006, AM J KIDNEY DIS, V47, P88, DOI 10.1053/j.ajkd.2005.09.023
  5. BOMBARDIER C, 1992, ARTHRITIS RHEUM, V35, P630, DOI 10.1002/art.1780350606
  6. Bostrom MA, 2010, CLIN J AM SOC NEPHRO, V5, P1107, DOI 10.2215/CJN.08721209
  7. Buhaescu I, 2007, SEMIN ARTHRITIS RHEU, V36, P224, DOI 10.1016/j.semarthrit.2006.09.002
  8. Cardena MMSG, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0062005
  9. Chen Z, 2012, J AM SOC NEPHROL, V23, p136A
  10. Churg J, 1995, RENAL DIS CLASSIFICA
  11. Estrella MM, 2012, J AM SOC NEPHROL, V23, p248A
  12. Franceschini N, 2010, HUM GENET, V127, P295, DOI 10.1007/s00439-009-0769-8
  13. Freedman BI, 2010, AM J NEPHROL, V32, P66, DOI 10.1159/000314688
  14. Freedman BI, 2009, KIDNEY INT, V75, P736, DOI 10.1038/ki.2008.701
  15. Genovese G, 2013, NAT REV NEPHROL, V9, P240, DOI 10.1038/nrneph.2013.34
  16. Genovese G, 2010, KIDNEY INT, V78, P698, DOI 10.1038/ki.2010.251
  17. Hays T, 2012, AIDS, V26, P797, DOI 10.1097/QAD.0b013e328351f6cf
  18. Hoy WE, 2012, J AM SOC NEPHROL, V23, p77A
  19. Johnstone DB, 2011, MOL CELL BIOL, V31, P2162, DOI 10.1128/MCB.05234-11
  20. Kanji Z, 2011, J AM SOC NEPHROL, V22, P2091, DOI 10.1681/ASN.2010121234
  21. Kao WHL, 2008, NAT GENET, V40, P1185, DOI 10.1038/ng.232
  22. Kopp JB, 2008, NAT GENET, V40, P1175, DOI 10.1038/ng.226
  23. Larsen CP, 2013, J AM SOC NEPHROL, V24, P722, DOI 10.1681/ASN.2012121180
  24. LEVEY AS, 1992, ANN INTERN MED, V116, P114
  25. Lin CP, 2012, GENES IMMUN, V13, P232, DOI 10.1038/gene.2011.82
  26. Matsha TE, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0052529
  27. MILLER SA, 1988, NUCLEIC ACIDS RES, V16, P1215, DOI 10.1093/nar/16.3.1215
  28. Monajemi H, 2002, GENOMICS, V79, P539, DOI 10.1006/geno.2002.6729
  29. Muller T, 2011, KIDNEY INT, V80, P1055, DOI 10.1038/ki.2011.256
  30. O'Toole JF, 2012, J AM SOC NEPHROL, V23, p323A
  31. Papeta N, 2011, J AM SOC NEPHROL, V22, P1991, DOI 10.1681/ASN.2011040434
  32. Sanchez E, 2012, ARTHRITIS RHEUM-US, V64, P3687, DOI 10.1002/art.34650
  33. TAN EM, 1982, ARTHRITIS RHEUM, V25, P1271, DOI 10.1002/art.1780251101
  34. Tzur S, 2010, HUM GENET, V128, P345, DOI 10.1007/s00439-010-0861-0
  35. Zhang YF, 2012, BLOOD, V119, P238, DOI 10.1182/blood-2011-06-358853