Dataset Information

SCUBE3 Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.

ABSTRACT: Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic disposition with more than 100 susceptibility genes identified until now. However, our knowledge on SLE genetic background is still limited. The present study was aimed at evaluating the role of single nucleotide polymorphisms (SNPs) in SCUBE3, a TGF-? signaling activator, with SLE susceptibility in Chinese populations.

Methods: A total of 2801 individuals (490 cases and 493 controls from GWAS cohort and 1003 cases and 815 controls from our cohort) were enrolled, and SNPs located 10?kb up- and downstream of SCUBE3 (chr6:35182190-35218609) were included in the genetic association study. Multiple layers of bioinformatics were conducted, and the levels of SCUBE3 expression were confirmed.

Results: Of the 31 SNPs in SCUBE3 tested, 24 SNPs were significantly associated with SLE at p ? 0.05. The top locus was rs1888822 with p = 8.74?10^-6 in the discovery cohort and was confirmed by the replication cohort with p = 0.012. Additionally, the levels of SCUBE3 mRNA expression were significantly lower in patients with SLE comparing with healthy controls (p = 4.28?10^-4). Further expression data from ArrayExpress showed that the expression of SCUBE3 was also lower in CD3⁺ T cells and B cells from patients with SLE.

Conclusions: Our research revealed that variants in SCUBE3, which encode SCUBE3 as a TGF-? signaling activator, can be considered as a new genetic susceptibility factor for systemic lupus erythematosus. And the reduced mRNA expression of SCUBE3 was first reported in patients with SLE.

SUBMITTER: Qi YY

PROVIDER: S-EPMC7683159 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>SCUBE3</i> Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.

Qi Yuan-Yuan YY Zhao Ya-Fei YF Zhai Ya-Ling YL Zhang Xiao-Xue XX Wang Xiao-Yang XY Liu Xina-Ran XR Cui Yan Y Ning Xiang-Hui XH Zhao Zhan-Zheng ZZ

Journal of immunology research 20201114

<h4>Background</h4>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic disposition with more than 100 susceptibility genes identified until now. However, our knowledge on SLE genetic background is still limited. The present study was aimed at evaluating the role of single nucleotide polymorphisms (SNPs) in <i>SCUBE3</i>, a TGF-<i>β</i> signaling activator, with SLE susceptibility in Chinese populations.<h4>Methods</h4>A total of 2801 individuals (490 cases and ...[more]

PMID: 33274247

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Project description:Background and objectivesOne hypothesis states that IgA nephropathy (IgAN) is a syndrome with an autoimmune component. Recent studies strongly support the notion of shared genetics between immune-related diseases. This study investigated single-nucleotide polymorphisms (SNPs) reported to be associated with systemic lupus erythematosus (SLE) in a Chinese cohort of patients with IgAN and in controls.Design, setting, participants, & measurementsThis study investigated whether SNP markers that had been reported to be associated with SLE were also associated with IgAN in a Chinese population. The study cohort consisted of 1194 patients with IgAN and 902 controls enrolled in Peking University First Hospital from 1997 to 2008.ResultsNinety-six SNPs mapping to 60 SLE loci with reported P values <1 × 10(-5) were investigated. CFH (P=8.41 × 10(-6)), HLA-DRA (P=4.91 × 10(-6)), HLA-DRB1 (P=9.46 × 10(-9)), PXK (P=3.62 × 10(-4)), BLK (P=9.32 × 10(-3)), and UBE2L3 (P=4.07 × 10(-3)) were identified as shared genes between IgAN and SLE. All associations reported herein were corroborated by associations at neighboring SNPs. Many of the alleles that are risk alleles for SLE are protective alleles for IgAN. By analyses of two open independent expression quantitative trait loci (eQTL) databases, correlations between genotypes and corresponding gene expression were observed (P<0.05 in multiple populations), suggesting a cis-eQTL effect. From gene-expression databases, differential expressions of these genes were observed in IgAN. Additive interactions between PXK rs6445961 and HLA-DRA rs9501626 (P=1.51 × 10(-2)), as well as multiplicative interactions between CFH rs6677604 and HLA-DRB1 rs9271366 (P=1.77 × 10(-2)), and between HLA-DRA rs9501626 and HLA-DRB1 rs9271366 (P=3.23 × 10(-2)) were observed. Disease risk decreased with accumulation of protective alleles. Network analyses highlighted four pathways: MHC class II antigen presentation, complement regulation, signaling by the B-cell receptor, and ubiquitin/proteasome-dependent degradation.ConclusionFrom this "systems genetics" perspective, these data provide important clues for future studies on pleiotropy in IgAN and lupus nephritis.

Dataset Information

SCUBE3 Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.

Publications

<i>SCUBE3</i> Is Likely a Susceptibility Gene for Systemic Lupus Erythematosus for Chinese Populations.

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