title: MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus nephritis from an admixture population.
abstract: 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.
authors.affiliation: Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Vinícius Sardão
authors.initials: VS
authors.lastname: Colares
authors.affiliation: Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Silvia Maria de Oliveira
authors.initials: SM
authors.lastname: Titan
authors.affiliation: Molecular Cardiology Laboratory, Heart Institute (InCor), Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Alexandre da Costa
authors.initials: Ada C
authors.lastname: Pereira
authors.affiliation: Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Malafronte
authors.affiliation: Department of Legal Medicine, Ethics and Occupational Health, Medical School, University of São Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Mari M
authors.initials: MM
authors.lastname: Cardena
authors.affiliation: Laboratory of Human Genetics and Medicine, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Sidney
authors.initials: S
authors.lastname: Santos
authors.affiliation: Molecular Cardiology Laboratory, Heart Institute (InCor), Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Department of Legal Medicine, Ethics and Occupational Health, Medical School, University of São Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Cíntia
authors.initials: C
authors.lastname: Fridman
authors.affiliation: Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Rui Toledo
authors.initials: RT
authors.lastname: Barros
authors.affiliation: Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Viktória
authors.initials: V
authors.lastname: Woronik
mesh_terms: D000328:Adult; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D001938:Brazil; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000235:genetics*; D008181:Lupus Nephritis / Q000150:complications / Q000235:genetics*; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000235:genetics*
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains