RANK/RANKL/OPG axis genes relation to cognitive impairment in children with transfusion-dependent thalassemia: a cross-sectional study.

Background: RANK/RANKL/OPG axis was implicated in many pathological conditions. The study aimed to assess the relationship between the studied RANK, RANKL, and OPG polymorphisms and alleles and cognitive impairment in children with transfusion-dependent thalassemia (TDT).

Methods: This study included 60 TDT children. Real-time PCR was done for: rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, rs9594782 and rs2277438 polymorphisms for the RANKL gene, and rs207318 polymorphism for the OPG gene. The intelligence quotient (IQ) was assessed using the Wechsler Intelligence Scale for Children-Third Edition.

Results: TDT children had a low average total IQ, verbal IQ, and borderline performance IQ. RANK rs1805034 (C > T) had a significant effect on total IQ (p = 0.03). Its TT polymorphism and the CT polymorphism of RANKL rs9494782 (C > T) had a significantly lower total IQ (p = 0.01 for both). The G allele of the RANKL rs2277438 (G > A) had a significantly lower total IQ (p = 0.02). RANK rs1805034 (C > T) and RANKL rs2277438 (G > A) significantly affected verbal IQ (p = 0.01 and 0.03). TT genotype of RANK rs1805034 (C > T) had significantly lower verbal IQ (p = 0.002). Furthermore, the GG genotype of RANKL rs2277438 (G > A) had a significantly lower verbal and performance IQ than the AA genotype (p = 0.04 and 0.01 respectively), and its G allele had a significantly lower performance IQ than the A allele (p = 0.02).

Conclusion: TDT children had low average total and verbal IQ while their performance IQ was borderline. The RANK/RANKL/OPG pathway affects cognition in TDT children, as some of the studied genes' polymorphisms and alleles had significant effects on total, verbal, and performance IQ of the studied TDT children.