Association of ABCC2 Gene Polymorphism (rs3740066) with Thalidomide-Induced Peripheral Neuropathy in Transfusion-Dependent β-Thalassemia Patients: A Case–Control Study from Pakistan
DOI:
https://doi.org/10.52206/jsmc.2025.15.4.1405Abstract
Background: Thalidomide has re-emerged as a potential fetal hemoglobin (HbF) inducer
for transfusion-dependent β-thalassemia (TDT). However, its clinical use is limited by
thalidomide-induced peripheral neuropathy (TIPN), a frequent and sometimes irreversible
adverse effect. Genetic variations in the ABCC2 gene may influence susceptibility to TIPN,
yet evidence in thalassemia patients is scarce.
Objective: To assess the frequency and severity of TIPN and explore its association with
ABCC2 single-nucleotide polymorphism (SNP) rs3740066 among Pakistani TDT patients.
Methodology: A case–control study was conducted on 102 TDT patients who received
thalidomide (1.5 mg/kg/day) for at least six months. Patients diagnosed with TIPN per the
National Cancer Institute Common Terminology Criteria for Adverse Events (Version 5.0)
were classified as cases (n = 51), and those without neuropathy as controls (n = 51). Blood
samples were collected for DNA extraction, and genotyping was performed using Sanger
sequencing.
Results: Among cases, 72% had Grade 1, 22% Grade 2, and 6% Grade 3 neuropathy.
Logistic regression revealed a significant association between TIPN and female gender (β =
1.271, p = 0.008, OR = 3.56, 95% CI: 1.39–9.08). No significant association was found
between ABCC2 genotypes and TIPN (p > 0.05).
Conclusion: Female gender was a significant predictor of TIPN, whereas ABCC2 rs3740066
polymorphism showed no significant association. These findings suggest that non-genetic
factors, such as gender-related biological differences, may contribute more strongly to TIPN
risk than this genetic variant.
Keywords: ABCC2 gene, Peripheral neuropathy, rs3740066, Thalidomide, Transfusiondependent β-thalassemia.
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