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Int J Rheum Dis. 2019 May;22(5):905-912. doi: 10.1111/1756-185X.13515. Epub 2019 Mar 12.

Glycoprotein 96 polymorphisms are associated with the risk of systemic lupus erythematosus: A case-control study.

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Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
College of Pharmacy, Yonsei University, Incheon, Korea.
Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
Biotechnology 2 Institute, Celltrion Inc., Incheon, Korea.
Department of Statistics, Seoul National University, Seoul, Korea.



To investigate the clinical implications of a genetic polymorphism in glycoprotein 96 (GP96), by analyzing the association between the genotype and haplotype of GP96 with systemic lupus erythematosus (SLE).


We analyzed cell-surface expression of GP96 in peripheral blood mononuclear cells (PBMCs) and serum titer of anti-GP96 antibody of SLE patients. Single nucleotide polymorphisms and deletion mutants of GP96 were detected by two-dimensional gene scanning (TDGS). Odds ratios with 95% confidence intervals (CI) were determined for each genotype and haplotype through the chi-square test.


In total, 216 Korean SLE patients and 215 age- and sex-matched healthy controls were enrolled. In SLE patients, as opposed to healthy controls, cell-surface expression of GP96 among human leukocyte antigen-DR+ PBMCs (76.4% vs 45.5%, respectively, P < 0.001) and serum anti-GP96 antibody titers (0.98 vs 0.50, respectively, P = 0.012) increased. TDGS revealed six polymorphic sites in GP96, two of which were significantly associated with SLE (exon 1, g.-7C>G, odds ratio [OR] 1.78, 95% CI 1.16-2.75, P = 0.009; exon 17, g.17009_17011del, OR 1.76, 95% CI 1.18-2.64, P = 0.006). Two haplotypes (121111, 211212) were strongly associated with SLE (OR 8.92, 95% CI 1.10-72.6, P = 0.041; OR 3.03, 95% CI 1.22-7.50, P = 0.017, respectively) and specific clinical manifestations (discoid rash, arthritis, renal disorder, neurologic disorder, and hematologic disorder). Haplotype-based analysis revealed a stronger association between GP96 and SLE than did genotype-based analysis.


The two polymorphisms, each in exons 1 and 17 of GP96 are potential genetic risk factors of SLE. Two haplotypes 121111 and 211212 are related to not only SLE but also specific clinical manifestations.


GP96; heat shock protein; single nucleotide polymorphism; systemic lupus erythematosus; two-dimensional gene scanning


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