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. 2024 Dec 19:17:6343-6353.
doi: 10.2147/IJGM.S489870. eCollection 2024.

Sex-Biased CD3ζ 3'-UTR SNP Increased Incidence Risk in Aplastic Anemia

Lixing Guo #  1 , Yuping Zhang #  2 , Xiaoen Liu #  3 , Yankai Xiao #  3 , Weifeng Luo  4 , Su Fang  5 , Yan Li  6 , Jing Lai  7 , Yangqiu Li  3   7 , Bo Li  3
Affiliations

Sex-Biased CD3ζ 3'-UTR SNP Increased Incidence Risk in Aplastic Anemia

Lixing Guo et al. Int J Gen Med. .

Abstract

Purpose: Aplastic anemia (AA) is a bone marrow failure syndrome with an unclear pathogenesis. Abnormal T cell immunity is one of the mechanisms involved in AA, and CD3ζ is an important signaling molecule for T cell activation. Single-nucleotide polymorphisms (SNPs) in CD3ζ 3'-untranslated region (3'-UTR) were associated with some immune-related disease occurrence and affect CD3ζ protein level. In this study, our aim was to analyze whether CD3ζ 3'-UTR SNPs were associated with AA susceptibility and had influence on CD3ζ protein level and provide new research data for exploring the pathogenesis of aplastic anemia.

Patients and methods: We screened the genotypes of SNPs in 101 healthy individuals and 91 AA patients by PCR-RFLP and sequencing. In addition, the effect of specific CD3ζ 3'-UTR SNPs was analyzed by flow cytometry and dual luciferase assay.

Results: Four SNPs of CD3ζ 3'-UTR, 1184 C >G (rs3738212), 1292 delG (rs3831958), 1403 G >C (rs1052230) and 1410 A >T (rs1052231) were identified from Chinese healthy individuals and AA patients in which rs3738212 was not previously reported. Increased risk of AA was observed in female AA who with heterozygous genotype of linkage disequilibrium SNP (rs3831958, rs1052230 and rs1052231). Different genotypes of rs3738212 have sex-biases feature in AA, higher 1184 CC frequency in male AA and higher 1184 CG frequency in female AA. Furthermore, rs3738212 could upregulate CD3ζ protein level.

Conclusion: This study first identified sex-specific CD3ζ 3'-UTR SNPs that were associated with risk of AA. Our data also demonstrated that rs3738212 could upregulate CD3ζ protein level.

Keywords: CD3ζ 3ʹ-untranslated region; CD3ζ protein level; aplastic anemia; single-nucleotide polymorphisms.

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Conflict of interest statement

The authors declare that they have no competing interests in this work.

Figures

Figure 1
Figure 1
Characteristic of SNPs in CD3ζ 3ʹ-UTR from Chinese HIs and AA.
Figure 2
Figure 2
The genotype characteristic of SNPs, rs3738212, rs3831958, rs1052230 and rs1052231 among NSAA, SAA and VSAA.
Figure 3
Figure 3
The feature of CD3ζ 3ʹ-UTR SNPs in different sex from HIs and AA.
Figure 4
Figure 4
The feature of CD3ζ 3ʹ-UTR SNPs in different sex of AA with different severities.
Figure 5
Figure 5
The effect of rs3738212 on CD3ζ protein level.
See this image and copyright information in PMC

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