Impact of TMPRSS6 gene polymorphism on iron overload among children with sickle cell disease.

Abstract

Objective/background: Iron overload is a significant problem in transfusion-dependent children with sickle cell disease (SCD). The molecular mechanisms underlying the progression to iron overload in SCD are poorly understood. Our aim is to investigate how TMPRSS6 single nucleotide polymorphisms (SNPs) affect iron status in children with SCD.

Methods: A case-control study was conducted for 61 SCD children, aged 6-18 years, and a control group of 42 age-sex matched healthy children. Real time polymerase chain reaction (PCR) was performed to determine the SNPs of rs11704654 C/T, rs4820268 A/G and rs855791 A/G of TMPRSS6 gene and iron overload parameters were measured.

Results: There was a significant protective association between SCD and the rs11704654 polymorphism (OR [95% CI)] = 0.36(0.15-0.86), P < 0.05. In contrast, a significant association between rs4820268, rs855791 polymorphisms and SCD risk was found, using the dominant genetic model (P < 0.05). The hepcidin gene expression and hepcidin/iron ratio were significantly higher in rs4820268 AG genotype compared to the minor homozygote GG genotype. Meanwhile, there was no significant difference between rs11704654, rs855791 genotypes and iron status parameters.

Conclusion: TMPRSS6 gene polymorphism influences susceptibility to SCD and contributes to the regulation of iron status. The rs4820268 AG genotype provides protection against iron overload. Modulation of iron status by TMPRSS6 SNPs represents a promising target for future therapy.