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

Jeong Seok Lee, Churl Hyun Im, Sang Jin Lee, Ji Yong Choi, Jung Min Han, Sunghoon Kim, Dong Jo Kim, Taesung Park, Eun Young Lee, Yeong Wook Song

Research output: Contribution to journalArticle

Abstract

Aim: 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). Method: 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. Results: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)905-912
Number of pages8
JournalInternational Journal of Rheumatic Diseases
Volume22
Issue number5
DOIs
Publication statusPublished - 2019 May

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All Science Journal Classification (ASJC) codes

  • Rheumatology

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