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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.

Author information

1
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
2
College of Pharmacy, Yonsei University, Incheon, Korea.
3
Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
4
Biotechnology 2 Institute, Celltrion Inc., Incheon, Korea.
5
Department of Statistics, Seoul National University, Seoul, Korea.

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.

KEYWORDS:

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

PMID:
30860673
DOI:
10.1111/1756-185X.13515

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