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Background <p>The <i>PTPN22</i> gene encodes Lyp, a phosphatase involved in downregulating T-cell receptor signaling and modulating immune homeostasis. Although <i>PTPN22</i> polymorphisms rs2476601 (R620W) and rs33996649 (R263Q) are associated with autoimmune diseases, their role in infectious diseases such as tuberculosis susceptibility remains unclear.</p> Objective <p>To evaluate the association of <i>PTPN22</i> polymorphisms with TB susceptibility and assess their functional relevance through gene expression profiling in a South Asian cohort.</p> Methodology <p><i>PTPN22</i> polymorphisms and expression in 111&#xa0;TB patients and 85 controls were analyzed by ARMS-PCR and RT-qPCR, with association and predictive analyses performed using logistic regression, ROC, LD (Haploview), and SPSS v26.</p> Results <p>A significant association was observed between the rs33996649 C/T genotype and increased TB susceptibility (<i>p</i> &lt; 0.008; OR = 5.87), while no significant association was found for rs2476601. Logistic regression indicating a stronger contribution to TB risk for rs33996649 (1.1279) compared to rs2476601 (0.2276). ROC curve analysis yielded an area under the curve (AUC) of 0.63, suggesting good predictive power for the combined genetic model. Linkage disequilibrium analysis demonstrated low correlation between the SNPs (D′ ≈ 0.40, r2 ≈ 0), indicating independent inheritance. <i>PTPN22</i> expression was modestly upregulated in TB patients (mean fold change = 1.2 vs. 1.0 in controls), though the difference was not statistically significant (<i>p </i>&gt; 0.05), possibly reflecting compensatory immune regulation in variant carriers.</p> Conclusion <p>The <i>PTPN22</i> rs33996649 (R263Q) variant shows a significant independent association with TB susceptibility, highlighting its role as a genetic risk factor and potential target for immunogenetic research.</p>

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Role of the PTPN22 C1858T (R263Q) variant in tuberculosis susceptibility: genetic and functional evidence from a South Asian cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月3日

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  • Fasihat ul Ain,
  • Faheem Shahzad,
  • Shah Jahan,
  • Khursheed Javed,
  • Romeeza Tahir,
  • Hasnain Javed,
  • Rabia Siddiqua

摘要

Background

The PTPN22 gene encodes Lyp, a phosphatase involved in downregulating T-cell receptor signaling and modulating immune homeostasis. Although PTPN22 polymorphisms rs2476601 (R620W) and rs33996649 (R263Q) are associated with autoimmune diseases, their role in infectious diseases such as tuberculosis susceptibility remains unclear.

Objective

To evaluate the association of PTPN22 polymorphisms with TB susceptibility and assess their functional relevance through gene expression profiling in a South Asian cohort.

Methodology

PTPN22 polymorphisms and expression in 111 TB patients and 85 controls were analyzed by ARMS-PCR and RT-qPCR, with association and predictive analyses performed using logistic regression, ROC, LD (Haploview), and SPSS v26.

Results

A significant association was observed between the rs33996649 C/T genotype and increased TB susceptibility (p < 0.008; OR = 5.87), while no significant association was found for rs2476601. Logistic regression indicating a stronger contribution to TB risk for rs33996649 (1.1279) compared to rs2476601 (0.2276). ROC curve analysis yielded an area under the curve (AUC) of 0.63, suggesting good predictive power for the combined genetic model. Linkage disequilibrium analysis demonstrated low correlation between the SNPs (D′ ≈ 0.40, r2 ≈ 0), indicating independent inheritance. PTPN22 expression was modestly upregulated in TB patients (mean fold change = 1.2 vs. 1.0 in controls), though the difference was not statistically significant (p > 0.05), possibly reflecting compensatory immune regulation in variant carriers.

Conclusion

The PTPN22 rs33996649 (R263Q) variant shows a significant independent association with TB susceptibility, highlighting its role as a genetic risk factor and potential target for immunogenetic research.