In:
Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 11 ( 2017-11), p. 3383-3394
Abstract:
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 ( P omnibus 〈 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 ( P omnibus 〈 0.001), HLA-DPβ1 amino acid 76 ( P omnibus 〈 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.
Type of Medium:
Online Resource
ISSN:
1046-6673
,
1533-3450
DOI:
10.1681/ASN.2016121331
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2029124-3
