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MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus nephritis from an admixture population

Vinícius Sardão Colares1, Silvia Maria de Oliveira Titan1, Alexandre da Costa Pereira2

  • 1Nephrology Division, Hospital das Clínicas, Sao Paulo University Medical School, Sao Paulo, Sao Paulo, Brazil.

Plos One
|March 25, 2014
PubMed

Insights

MYH9 gene variants, not APOL1, increase chronic kidney disease (CKD) risk in lupus nephritis (LN) patients. Specific MYH9 polymorphisms and the E1 haplotype are linked to higher CKD progression, independent of ancestry.

Area of Science:

  • Nephrology
  • Genetics
  • Immunology

Background:

  • MYH9 gene polymorphisms are linked to chronic kidney disease (CKD) risk, particularly in non-diabetic nephropathy, HIV nephropathy, and FSGS.
  • While APOL1 gene variants are also associated with CKD, especially in individuals of African ancestry, their interplay with MYH9 requires further investigation.
  • The genetic contribution to CKD in lupus nephritis (LN) remains incompletely understood, necessitating studies on specific gene variants.

Purpose of the Study:

  • To investigate the association of MYH9 and APOL1 gene polymorphisms with CKD risk in Brazilian patients with lupus nephritis (LN).
  • To determine if MYH9 or APOL1 genetic variants are independent risk factors for CKD progression in this specific patient cohort.
  • To clarify the role of MYH9 and APOL1 in the pathogenesis of CKD in LN, considering genetic ancestry.

Main Methods:

  • A retrospective analysis of 196 lupus nephritis patients was conducted.
  • Specific MYH9 (rs4821480, rs2032487, rs4821481, rs3752462) and APOL1 (rs73885319, rs16996616, rs60910145, rs71785313) polymorphisms were genotyped.
  • Genetic ancestry was assessed using autosomal and mitochondrial DNA analysis. The primary outcome was a doubling of serum creatinine or end-stage renal disease.

Main Results:

  • MYH9 and APOL1 polymorphisms were not found to be in linkage disequilibrium (LD) in this population.
  • No significant association was observed between APOL1 polymorphisms and the primary outcome.
  • The MYH9 rs3752462 polymorphism showed a positive association with CKD progression (HR 3.72).
  • Carriers of the MYH9 E1 haplotype (GCCT) demonstrated a significant association with increased CKD risk (HR 2.0), even after adjusting for covariates.

Conclusions:

  • MYH9 gene polymorphisms, specifically rs3752462 and the E1 haplotype, are associated with an increased risk of CKD progression in Brazilian lupus nephritis patients.
  • APOL1 gene polymorphisms were not found to be associated with CKD risk in this cohort.
  • These findings suggest that MYH9 variants contribute to CKD risk in LN independently of genetic ancestry or race.

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