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Background <p>Recurrent spontaneous abortion (RSA) is defined, according to the 2023 ESHRE guideline, as the loss of two or more clinically recognized pregnancies before 24 completed weeks of gestation. An imbalance of pro-inflammatory cytokines, particularly interleukin-17A (IL-17A) produced by T-helper-17 cells, has been implicated in the pathophysiology of RSA. The present case–control study aimed to investigate the association between the IL-17A rs2275913 (–197G &gt; A) single-nucleotide polymorphism, circulating serum IL-17A concentrations, and RSA in Iraqi women.</p> Materials and methods <p>Sixty women with a history of two or more consecutive clinical miscarriages and 60 age- and BMI-matched apparently healthy women with at least one prior uneventful live birth and no history of miscarriage were enrolled between September 2025 and January 2026 from two referral centres in Najaf, Iraq. Genomic DNA was extracted from peripheral blood using the salting-out technique. Genotyping of rs2275913 was performed by tetra-primer amplification-refractory mutation system PCR (T-ARMS-PCR), and 10% of samples were re-genotyped and confirmed by Sanger sequencing with 100% concordance. Serum IL-17A was quantified by a commercial sandwich ELISA (Elabscience Biotechnology Inc., Houston, TX, USA; catalog no. E-EL-H0105), with all samples run in duplicate. Hardy–Weinberg equilibrium (HWE), allelic/genotypic frequencies, odds ratios (OR) with 95% confidence intervals (CI) under codominant, dominant, recessive, and allelic genetic models were computed, and multivariable logistic regression adjusted for age and BMI was performed using SPSS v26.0.</p> Results <p>Serum IL-17A concentrations were significantly higher in women with RSA than in controls (194.96 ± 81.67 pg/mL vs. 160.38 ± 33.69 pg/mL; <i>p</i> = 0.003). The frequency of the AA genotype of rs2275913 was significantly greater in RSA cases than in controls (53.3% vs. 0%; Fisher’s exact <i>p</i> &lt; 0.0001), as was the A allele frequency (70.0% vs. 25.8%; OR = 6.70, 95% CI 3.81–11.79, <i>p</i> &lt; 0.0001). Under the dominant genetic model (AA + AG vs. GG), carriers of the A allele had an approximately six-fold increased risk of RSA (OR = 6.08, 95% CI 2.47–14.96, <i>p</i> &lt; 0.001). The association remained significant after adjustment for age and BMI.</p> Conclusions <p>In this Iraqi cohort, the IL-17A rs2275913 A allele (particularly the AA genotype) and elevated serum IL-17A concentrations were significantly <i>associated</i> with RSA. These findings are consistent with a role for excessive Th17/IL-17-mediated pro-inflammatory signalling at the maternal–fetal interface. Because the control group departed from HWE and the sample size was modest, the findings require confirmation in larger, multi-centre populations before any clinical translation is considered.</p>

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Association of IL-17A rs2275913 polymorphism and serum IL-17A levels with recurrent spontaneous abortion in Iraqi women: a case-control study

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  • 发表日期：

    2026年5月11日

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  • Hawraa W. Joody AlFahham,
  • Taghreed F. Almahbobi,
  • Ahmed Hassan Kudhair

摘要

Background

Recurrent spontaneous abortion (RSA) is defined, according to the 2023 ESHRE guideline, as the loss of two or more clinically recognized pregnancies before 24 completed weeks of gestation. An imbalance of pro-inflammatory cytokines, particularly interleukin-17A (IL-17A) produced by T-helper-17 cells, has been implicated in the pathophysiology of RSA. The present case–control study aimed to investigate the association between the IL-17A rs2275913 (–197G > A) single-nucleotide polymorphism, circulating serum IL-17A concentrations, and RSA in Iraqi women.

Materials and methods

Sixty women with a history of two or more consecutive clinical miscarriages and 60 age- and BMI-matched apparently healthy women with at least one prior uneventful live birth and no history of miscarriage were enrolled between September 2025 and January 2026 from two referral centres in Najaf, Iraq. Genomic DNA was extracted from peripheral blood using the salting-out technique. Genotyping of rs2275913 was performed by tetra-primer amplification-refractory mutation system PCR (T-ARMS-PCR), and 10% of samples were re-genotyped and confirmed by Sanger sequencing with 100% concordance. Serum IL-17A was quantified by a commercial sandwich ELISA (Elabscience Biotechnology Inc., Houston, TX, USA; catalog no. E-EL-H0105), with all samples run in duplicate. Hardy–Weinberg equilibrium (HWE), allelic/genotypic frequencies, odds ratios (OR) with 95% confidence intervals (CI) under codominant, dominant, recessive, and allelic genetic models were computed, and multivariable logistic regression adjusted for age and BMI was performed using SPSS v26.0.

Results

Serum IL-17A concentrations were significantly higher in women with RSA than in controls (194.96 ± 81.67 pg/mL vs. 160.38 ± 33.69 pg/mL; p = 0.003). The frequency of the AA genotype of rs2275913 was significantly greater in RSA cases than in controls (53.3% vs. 0%; Fisher’s exact p < 0.0001), as was the A allele frequency (70.0% vs. 25.8%; OR = 6.70, 95% CI 3.81–11.79, p < 0.0001). Under the dominant genetic model (AA + AG vs. GG), carriers of the A allele had an approximately six-fold increased risk of RSA (OR = 6.08, 95% CI 2.47–14.96, p < 0.001). The association remained significant after adjustment for age and BMI.

Conclusions

In this Iraqi cohort, the IL-17A rs2275913 A allele (particularly the AA genotype) and elevated serum IL-17A concentrations were significantly associated with RSA. These findings are consistent with a role for excessive Th17/IL-17-mediated pro-inflammatory signalling at the maternal–fetal interface. Because the control group departed from HWE and the sample size was modest, the findings require confirmation in larger, multi-centre populations before any clinical translation is considered.