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Several genetic variants associated with systemic sclerosis in a Chinese Han population

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Abstract

Background

Systemic sclerosis (SSc) is a connective tissue disease with ethnic differences. Single-nucleotide polymorphisms (SNPs) in the ARID3A, CXCR5, and TNFSF8 genes have been reported to be associated with various autoimmune diseases. The aim of this study was to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population.

Methods

A case–control study was conducted in 342 patients with SSc and 694 ethnically matched healthy controls. SNPs in ARID3A, CXCR5, and TNFSF8 were genotyped using a Sequenom MassArray iPLEX system, and allele association analyses were performed using the PLINK v1.90 software.

Results

Our study demonstrated that the ARID3A rs10415976 G and CXCR5 rs77871618 T alleles were suggestively associated with patients with SSc (P = 0.049 and P = 0.024, respectively) and TNFSF8 rs1555457 T allele was strongly associated with SSc (P = 0.003). Patients carrying the ARID3A rs350146 TT and TNFSF8 rs1555457 TT genotypes had a significant increased risk of SSc (P = 0.03 and P = 0.004, respectively). Moreover, rs10415976, rs77871618, and rs1555457 were associated with SSc in an additive genetic model (P < 0.05). rs62132345 and rs1555457 were associated with SSc in the dominant genetic model (P < 0.05). rs350146 was associated with SSc in the recessive genetic model (P = 0.029).

Conclusions

ARID3A rs10415976, ARID3A rs350146, and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population in this study.

Key Points

• This case-control study determined that ARID3A rs10415976, ARID3A rs350146 and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population.

• The differences in these results compared with previous studies may be a result of ethnic and racial differences.

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Data availability

Not applicable.

Abbreviations

ARID:

A-T-rich interaction domain

CI:

Confidence interval

GWAS:

Genome-wide association study

HWE:

Hardy-Weinberg equilibrium

ILD:

Interstitial lung disease

IPF:

Idiopathic pulmonary fibrosis

OR:

Odds ratio

PAH:

Pulmonary arterial hypertension

PBC:

Primary biliary cholangitis

PCR:

Polymerase chain reaction

PUMCH:

Peking Union Medical College Hospital

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

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Funding

This research was supported by the grants from the National Key Research and Development Program of China (Grants 2018YFE0207300) and the National Natural Science Foundation of China (Grants 81871302). This work was supported by Beijing Key Clinical Specialty for Laboratory Medicine—Excellent Project (No. ZK201000).

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Author notes

  1. Chenxi Liu and Songxin Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, China

    Chenxi Liu, Songxin Yan, Haizhen Chen, Ziyan Wu, Liubing Li & Yongzhe Li

  2. Department of Clinical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

    Chenxi Liu

  3. Department of Clinical Laboratory, The First Hospital of Jilin University, Jilin, China

    Haizhen Chen

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  1. Chenxi Liu
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Contributions

CL wrote the manuscript. SY and HC conducted the study. ZW and LL prepared the materials. YL supported the research.

Corresponding author

Correspondence to Yongzhe Li.

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This study was approved by the ethics committee of the PUMCH, and informed consent was obtained from all the recruited participants.

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Liu, C., Yan, S., Chen, H. et al. Several genetic variants associated with systemic sclerosis in a Chinese Han population. Clin Rheumatol 42, 773–781 (2023). https://doi.org/10.1007/s10067-022-06409-3

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  • DOI: https://doi.org/10.1007/s10067-022-06409-3

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