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Background <p>Genetic predisposition is an important and fundamental determinant of susceptibility to rheumatoid arthritis (RA), a chronic autoimmune disease with joint deformity and disability. HLA-G plays an important role in the modulation of autoimmune disorders and inflammatory processes. The <i>HLA-G </i> + 3142G &gt; C and 14&#xa0;bp insertion/deletion variants have a controversial impact on pathogenesis of RA in various populations globally. The present study aimed to evaluate the possible association of <i>HLA-G </i>+ 3142 G &gt; C and 14-bp insertion/deletion variants with RA and to compare the concentration of soluble HLA-G in serum of RA patients and healthy controls.</p> Methodology <p>Two thirty RA patients and two fifty healthy controls fulfilling the ACR-EULAR/2010 criteria were included in this study. Genotyping of <i>HLA-G</i> + 3142G &gt; C and 14&#xa0;bp insertion/deletion variants was performed using PCR-RFLP and PCR-SSP methods, respectively. The concentration of soluble HLA-G was quantified using sHLA-G sandwich ELISA kit. Chi-squared test and unpaired t-test were employed for the analysis of categorical and continuous data, respectively, using SPSS 27.0. Bonferroni corrected <i>p</i> value &lt; 0.05 was considered as statistically significant.</p> Results <p>Significant difference in the genotype frequencies of <i>HLA-G </i>+ 3142G &gt; C variant was observed between RA patients and controls under codominant (GG versus GC: <i>p</i> = 0.009, OR = 1.817), dominant (GG versus GC + CC, <i>p</i> = 0.033, OR = 1.618) and over dominant (GG + CC versus GC: <i>p</i> = 0.002, OR = 1.847) inheritance models. Further, sHLA-G level was significantly reduced in RA patients as compared to controls (21.37 ± 10.53 ng/ml versus 29.83 ± 14.97 ng/ml, <i>p</i> &lt; 0.001).</p> Conclusion <p>The findings of this study reveal an association between + 3142G &gt; C variant of <i>HLA-G</i> gene and increased risk of RA in Indian Bengali population. Further, decreased sHLA-G concentration in RA patients in contrast to healthy controls indicates the dysregulation of immunoregulatory mechanism in RA. However, extensive study is warranted to evaluate the alteration of sHLA-G expression in response to therapy and autoantibody status of RA patients.</p>

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Human leukocyte antigen (HLA)-G gene + 3142G > C variant (rs1063320) confers susceptibility to rheumatoid arthritis in Indian Bengali population

  • 期刊论文

  • 发表日期：

    2025年9月27日

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  • Rajat Sarkar,
  • Animesh Chowdhury,
  • Subhasish Mandal,
  • Bappaditya Ghosh,
  • Manoj Lama

摘要

Background

Genetic predisposition is an important and fundamental determinant of susceptibility to rheumatoid arthritis (RA), a chronic autoimmune disease with joint deformity and disability. HLA-G plays an important role in the modulation of autoimmune disorders and inflammatory processes. The HLA-G  + 3142G > C and 14 bp insertion/deletion variants have a controversial impact on pathogenesis of RA in various populations globally. The present study aimed to evaluate the possible association of HLA-G + 3142 G > C and 14-bp insertion/deletion variants with RA and to compare the concentration of soluble HLA-G in serum of RA patients and healthy controls.

Methodology

Two thirty RA patients and two fifty healthy controls fulfilling the ACR-EULAR/2010 criteria were included in this study. Genotyping of HLA-G + 3142G > C and 14 bp insertion/deletion variants was performed using PCR-RFLP and PCR-SSP methods, respectively. The concentration of soluble HLA-G was quantified using sHLA-G sandwich ELISA kit. Chi-squared test and unpaired t-test were employed for the analysis of categorical and continuous data, respectively, using SPSS 27.0. Bonferroni corrected p value < 0.05 was considered as statistically significant.

Results

Significant difference in the genotype frequencies of HLA-G + 3142G > C variant was observed between RA patients and controls under codominant (GG versus GC: p = 0.009, OR = 1.817), dominant (GG versus GC + CC, p = 0.033, OR = 1.618) and over dominant (GG + CC versus GC: p = 0.002, OR = 1.847) inheritance models. Further, sHLA-G level was significantly reduced in RA patients as compared to controls (21.37 ± 10.53 ng/ml versus 29.83 ± 14.97 ng/ml, p < 0.001).

Conclusion

The findings of this study reveal an association between + 3142G > C variant of HLA-G gene and increased risk of RA in Indian Bengali population. Further, decreased sHLA-G concentration in RA patients in contrast to healthy controls indicates the dysregulation of immunoregulatory mechanism in RA. However, extensive study is warranted to evaluate the alteration of sHLA-G expression in response to therapy and autoantibody status of RA patients.