Association of an iron-related TMPRSS6 genetic variant c.2207 C>T (rs855791) with functional iron deficiency and its effect on multiple sclerosis risk in the South African population

Abstract

Methods. The study population consisted of 107 patients diagnosed with MS according to the McDonald criteria and 85 controls without neurological disease. DNA was extracted from all samples for genotyping of functional single nucleotide polymorphisms (SNPs) in the TMPRSS6 gene, c.2207C>T (rs855791). High-throughput real-time polymerase chain reaction (RT-PCR) methodology was applied using the Applied Biosystems (ABI) TaqMan assay, ABI 7900HT, following analytical validation against direct sequencing as the gold standard. Results. There were no significance differences in TMPRSS6 c.2207C>T variant frequency distributions between MS patients and controls (p=0.893). However, there was a significant difference between homozygosity for the iron-deficiency risk T allele and wild type C allele in the study population. Serum ferritin levels were significantly lower in patients than controls (p=0.001), with a significant difference between homozygous T allele and wild-type C allele (p=0.033). The T allele was consistent with lower levels of serum iron (p=0.014) and lower % transferrin saturation (p=0.039). In the MS group the T-allele was associated with an earlier age of diagnosis and presentation of first symptoms, although this was not statistically significant. Conclusion. These findings suggest that the c.2207C>T variant could contribute to increased risk for developing iron deficiency in MS. The results confirm the link between the TMPRSS6 genetic variant c.2207C>T and reduced iron levels in MS. Together with measurement of blood iron parameters, this could help identify a subgroup of MS patients with a lack of iron bioavailability, which may account for worsening of disease symptoms.