This Is MS Multiple Sclerosis Community: Knowledge & Support

Polymorphisms in the genes coding for iron binding and transporting proteins are associated with disability, severity, and early progression in multiple sclerosis

Donato Gemmati, Giulia Zeri, Elisa Orioli, Francesca E De Gaetano, Fabrizio Salvi, Ilaria Bartolomei, Sandra D’Alfonso, Claudia Dall’Osso, Maurizio A Leone, Ajay V Singh, Rosanna Asselta and Paolo Zamboni

BMC Medical Genetics 2012, 13:70 doi:10.1186/1471-2350-13-70
Published: 10 August 2012
Abstract (provisional)

Background

Iron involvement/imbalance is strongly suspected in multiple sclerosis (MS) etiopathogenesis, but its role is quite debated. Iron deposits encircle the veins in brain MS lesions, increasing local metal concentrations in brain parenchyma as documented by magnetic resonance imaging and histochemical studies. Conversely, systemic iron overload is not always observed. We explored the role of common single nucleotide polymorphisms (SNPs) in the main iron homeostasis genes in MS patients.

Methods

By the pyrosequencing technique, we investigated 414 MS cases [Relapsing-remitting (RR), n=273; Progressive, n=141, of which: Secondary (SP), n=103 and Primary (PP), n=38], and 414 matched healthy controls. Five SNPs in 4 genes were assessed: hemochromatosis (HFE: C282Y, H63D), ferroportin (FPN1: -8CG), hepcidin (HEPC: -582AG), and transferrin (TF: P570S).

Results

The FPN1-8GG genotype was overrepresented in the whole MS population (OR=4.38; 95%CI, 1.89-10.1; P<0.0001) and a similar risk was found among patients with progressive forms. Conversely, the HEPC -582GG genotype was overrepresented only in progressive forms (OR=2.53; 95%CI, 1.34-4.78; P=0.006) so that SP and PP versus RR yielded significant outputs (P=0.009). For almost all SNPs, MS disability score (EDSS), severity score (MSSS), as well as progression index (PI) showed a significant increase when comparing homozygotes versus individuals carrying other genotypes: HEPC -582GG (EDSS, 4.24+/-2.87 vs 2.78+/-2.1; P=0.003; MSSS, 5.6+/-3.06 vs 3.79+/-2.6; P=0.001); FPN1-8GG (PI, 1.11+/-2.01 vs 0.6+/-1.31; P=0.01; MSSS, 5.08+/-2.98 vs 3.85+/-2.8; P=0.01); HFE 63DD (PI, 1.63+/-2.6 vs 0.6+/-0.86; P=0.009). Finally, HEPC -582G-carriers had a significantly higher chance to switch into the progressive form (HR=3.55; 1.83-6.84; log-rank P=0.00006).

Conclusions

Polymorphisms in the genes coding for iron binding and transporting proteins, in the presence of local iron overload, might be responsible for suboptimal iron handling. This might account for the significant variability peculiar to MS phenotypes, particularly affecting MS risk and progression paving the way for personalized pharmacogenetic applications in the clinical practice.

First we need to see another study reproducing that correlation between venous flow irregularities and MS type. It was very interesting but we have not heard anything more along those lines in a long time.

there was a correlation between venous flow irregularities and MS type.

Conclusions

Polymorphisms in the genes coding for iron binding and transporting proteins, in the presence of local iron overload, might be responsible for suboptimal iron handling. This might account for the significant variability peculiar to MS phenotypes, particularly affecting MS risk and progression paving the way for personalized pharmacogenetic applications in the clinical practice.

I'd be more interested in finding out if serum iron levels do, or do not play a role.
I'm not sure if we can say "iron dysregulation" on the one hand, and "serum levels are irrelevant" on the other. If people with "iron overload" receive benefit from bloodletting, how do we not say that CCSVI would not benefit from the same thing?