IL-17A, IL-23R, FCGR3A are associated with neuropsychiatric systemic lupus erythematosus susceptibility in pediatric patients with lupus nephritis

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2025-02-03 DOI:10.1016/j.cyto.2025.156874

Chen Ye , Lizhi Chen , Lu Zhang , Yifan Zheng , Xiaohong Liu , Zhijun Huang , Kejing Tang , Xiaoyun Jiang , Pan Chen

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Abstract

Objective

To comprehensively investigate the impact of candidate loci on the susceptibility to neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort of Chinese children with lupus nephritis (LN).

Methods

This case-control study included sixty-two patients. And the case group consisted of 12 LN patients appearing NPSLE, while the control group consisted of 50 LN patients. A total of fifty-four single nucleotide polymorphisms (SNPs) across twenty genes were genotyped using the Agena Bioscience MassArray iPLEX platform. The associations between susceptibility to NPSLE and candidate SNPs were assessed using SNPStats online software. We evaluated the influence of candidate SNPs on the risk of NPSLE through odds ratios (OR) and 95 % confidence intervals (CI). Additionally, linkage disequilibrium (LD) and coefficient (D′ and r²) for haplotypes and their frequencies were performed using the genetic statistical online software SHEsis.

Results

Three significant SNPs were identified: IL17RA rs2895332, IL23R rs10889677, and FCGR3A rs396991. AA genotype of FCGR3A rs396991, GG genotype of IL17RA rs2895332 and AA genotype of IL23R rs10889677 exhibited a decreased risk of NPSLE compared to CA and CC genotypes, GA and AA genotypes, and CA and CC genotypes (rs396991 AA vs. CA-CC, OR 5.00, 95 %CI 0.99–25.17, P = 0.029; rs2895332 GG vs. GA-AA, OR 7.83, 95 %CI 1.47–41.79, P = 0.017; rs10889677 AA vs. CA-CC, OR 4.50, 95 %CI 1.08–18.69, P = 0.027). Furthermore, the haplotype A-T-G (STAT4 rs13426947, rs1551443 and rs3024866) appeared to confer protection against the development of NPSLE. The multivariate logistic regression analysis indicated that two specific SNPs were significantly associated with an increased risk of NPSLE: [FCGR3A rs396991 (OR = 6.444, 95 %CI = 1.1–37.736, P = 0.039), IL17RA rs2895332 (OR = 0.128, 95 %CI = 0.017–0.963, P = 0.046)]. Notably, the RegulomeDB score of them reached 1 f. Using HaploReg, these loci were in strong LD (r²>0.8) with several SNPs.

Conclusion

Our findings indicate that the polymorphisms IL17RA rs2895332, IL23R rs10889677, and FCGR3A rs396991 are significantly associated with the risk of NPSLE in childhood-onset LN.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.