Association Analysis of the MHC in Lupus Nephritis

J Am Soc Nephrol. 2017 Nov;28(11):3383-3394. doi: 10.1681/ASN.2016121331. Epub 2017 Jul 28.


Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRβ1 amino acid 11 (Pomnibus<0.001), HLA-DQβ1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPβ1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.

Keywords: Deep Sequencing; Major Histocompatibility Complex; Multiple Risk Variants; lupus nephritis.

MeSH terms

  • Adult
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Lupus Nephritis / genetics*
  • Major Histocompatibility Complex / genetics*
  • Male