Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

• DOI: 10.1681/asn.2013050446
• Publication Date: 2014-06-13T07:51:31Z
• Authors: Sharon A. Chung; Elizabeth E. Brown; Adrienne H. Williams; Paula S. Ramos; Celine C. Berthier; Tushar Bhangale; Marta E. Alarcon-...; Timothy W. Behrens; Lindsey A. Criswell; Deborah Cunningha...; F. Yesim Demirci; Jeffrey C. Edberg; Patrick M. Gaffney; John B. Harley; Chaim O. Jacob; M. Ilyas Kamboh; Jennifer A. Kelly; Susan Manzi; Kathy L. Moser-Si...; Laurie P. Russell; Michelle Petri; Betty P. Tsao; Tim J. Vyse; Raphael Zidovetzki; Matthias Kretzler; Robert P. Kimberly; Barry I. Freedman; Robert R. Graham; Carl D. Langefeld
• Keywords: Adult; 0303 health sciences; Adolescent; Genotype; 610; Middle Aged; Lupus Nephritis; Polymorphism, Single Nucleotide; White People; 3. Good health; Young Adult; 03 medical and health sciences; HLA-DR3 Antigen; Phenotype; 616; Humans; Lupus Erythematosus, Systemic; Female; Genetic Predisposition to Disease; HLA-DR2 Antigen; RNA, Messenger; Child; Aged; Genome-Wide Association Study

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. demonstrates familial aggregation accounts for significant morbidity mortality. We completed meta-analysis three genome-wide association studies to identify lupus nephritis-predisposing loci. Through genotyping imputation, >1.6 million markers were assessed in 2000 unrelated women European descent with (588 patients 1412 without nephritis). Tests computed using logistic regression adjusting population substructure. The strongest evidence was observed outside the MHC included localized 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 HLA-DR3, two well established susceptibility loci, showed (P=0.06 P=3.7×10(-5), respectively). Within class I region, rs9263871 (C6orf15-HCG22) had independent HLA-DR3 (P=8.5×10(-6)). Consistent functional role nephritis, intra-renal mRNA levels PDGFRA associated pathway members enrichment (n=32) compared controls (n=15). Results this large-scale investigation provide multiple biologically relevant