Linkage disequilibrium and haplotype effects of CD40 gene variants on romiplostim response in Iraqi patients with immune thrombocytopenia purpura
Aisha Muthanna Shanshal, Samer Imad Mohammed, Bassam Francis MattiAbstract:
BACKGROUND:
The CD40 polymorphism increases CD40 expression, leading to heightened pro-inflammatory cytokine levels, which contribute to immune thrombocytopenia (ITP) Purpura progression. Genetic variability influences drug-metabolizing enzymes and transporters, causing inter-individual differences in pharmacokinetics and pharmacodynamics. Consequences may result in disparities in treatment outcomes.
OBJECTIVES:
This study aimed to evaluate CD40 gene haplotypes, linkage disequilibrium (LD) patterns, and assess their association with the risk of non-response to romiplostim therapy in Iraqi ITP patients.
MATERIALS AND METHODS:
A descriptive cross-sectional design was carried out from May 1, 2025, to September 1, 2025, involving 78 ITP patients, who were selected according to the diagnostic criteria of the Iraqi hematologists consensus. It was conducted at the Hematology and Bone Marrow Transplant Center, Medical City, Baghdad, Iraq.
RESULTS:
LD tests showed strong association between (rs4810485 with rs1883832, rs997412137 and rs774291557), (rs1535045 with rs1883832 and rs774291557) with LD coefficient D’ equal 1, while the CD40 gene haplotype (T C T G A*) represents the highest frequency (0.36) of the five single-nucleotide polymorphisms with an odds ratio of 0.4, representing alleles that are non-mutant and may have a protective role in ITP disease in the current study. Whereas haplotype (T T C C T*) with a frequency of 1% may increase the risk of no response with an odds ratio of 10.17.
CONCLUSIONS:
CD40 gene haplotypes are strong determinants of romiplostim response in Iraqi ITP patients. These findings highlight the intricate genetic framework of therapy response and establish a basis for more extensive, confirmatory investigations focused on personalizing ITP care.