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<p>Aplastic anemia (AA) is a rare hematological disorder characterized by pancytopenia and bone marrow hypocellularity. Genetic variation in xenobiotic-metabolizing enzymes may influence disease risk, severity, and treatment outcomes. We investigated the association of CYP1A1 (m1/m4) and CYP2D6 (1934/2637) polymorphisms with susceptibility to AA, disease severity, and response to immunosuppressive therapy (IST). In this prospective case–control study, <i>n</i> = 200 patients with acquired AA and <i>n</i> = 200 age- and sex-matched controls were enrolled. Genotyping of CYP1A1 m1 (rs4646903), CYP1A1 m4 (rs1799814), CYP2D6 1934 (rs3892097/4), and CYP2D6 2637 (rs35742686/3) was performed using PCR-RFLP. Disease severity was categorized as non-severe (NSAA), severe (SAA), or very severe (VSAA), and treatment response was assessed after 6 months of IST. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The CYP1A1 m4 CA (OR = 1.99, <i>p</i> = 0.0026) and AA (OR = 3.05, <i>p</i> = 0.0379) genotypes were significantly associated with higher AA risk. The CYP2D6 1934 AA genotype also conferred increased susceptibility (OR = 2.08, <i>p</i> = 0.0463). Genotype–phenotype correlation revealed enrichment of CYP1A1 m4 CA and CYP2D6 1934 AG/AA genotypes in VSAA. In outcome analysis, both CYP1A1 m4 CA (<i>p</i> = 0.0219) and CYP2D6 1934 AA (<i>p</i> = 0.0264) were significantly associated with poor IST response. CYP1A1 m4 and CYP2D6 1934 polymorphisms may serve as predictive biomarkers for susceptibility, disease severity, and treatment response in AA, with potential implications for risk stratification and individualized therapy.</p>

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Impact of CYP1A1 and CYP2D6 Gene Polymorphisms on Susceptibility, Clinical Severity, and Treatment Response in Acquired Aplastic Anemia

  • 期刊论文

  • 发表日期：

    2026年1月12日

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  • Vijayta Singh,
  • Saurabh Shukla,
  • Anam Ahmed,
  • Alka Dwivedi,
  • Tabinda Hasan,
  • Hailah M. Almohaimeed,
  • Mohammad Idreesh khan,
  • Mirza Masroor Ali Beg,
  • Anil Kumar Tripathi

摘要

Aplastic anemia (AA) is a rare hematological disorder characterized by pancytopenia and bone marrow hypocellularity. Genetic variation in xenobiotic-metabolizing enzymes may influence disease risk, severity, and treatment outcomes. We investigated the association of CYP1A1 (m1/m4) and CYP2D6 (1934/2637) polymorphisms with susceptibility to AA, disease severity, and response to immunosuppressive therapy (IST). In this prospective case–control study, n = 200 patients with acquired AA and n = 200 age- and sex-matched controls were enrolled. Genotyping of CYP1A1 m1 (rs4646903), CYP1A1 m4 (rs1799814), CYP2D6 1934 (rs3892097/4), and CYP2D6 2637 (rs35742686/3) was performed using PCR-RFLP. Disease severity was categorized as non-severe (NSAA), severe (SAA), or very severe (VSAA), and treatment response was assessed after 6 months of IST. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The CYP1A1 m4 CA (OR = 1.99, p = 0.0026) and AA (OR = 3.05, p = 0.0379) genotypes were significantly associated with higher AA risk. The CYP2D6 1934 AA genotype also conferred increased susceptibility (OR = 2.08, p = 0.0463). Genotype–phenotype correlation revealed enrichment of CYP1A1 m4 CA and CYP2D6 1934 AG/AA genotypes in VSAA. In outcome analysis, both CYP1A1 m4 CA (p = 0.0219) and CYP2D6 1934 AA (p = 0.0264) were significantly associated with poor IST response. CYP1A1 m4 and CYP2D6 1934 polymorphisms may serve as predictive biomarkers for susceptibility, disease severity, and treatment response in AA, with potential implications for risk stratification and individualized therapy.