ArticleBMC medical genetics2012
Polymorphisms in the genes coding for iron binding and transporting proteins are associated with disability, severity, and early progression in multiple sclerosis.
Article in BMC medical genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Translational neurodegeneration · 2021Pooled it
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
- Epstein-Barr virus infection and vitamin D deficiency are both "causal" for multiple sclerosis (MS) - could the common denominator be their effects on hepcidin levels?Metabolic brain disease · 2025Review
- The role of activated partial thrombin time in mediating the impact of poorly glycemic control on diabetic peripheral neuropathy in patients with type 2 diabetes mellitus.Frontiers in endocrinology · 2025Article
- Review
- AI and ML-based risk assessment of chemicals: predicting carcinogenic risk from chemical-induced genomic instability.Frontiers in toxicology · 2024Review
- LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).Human genomics · 2023Article
- Semen Cryopreservation to Expand Male Fertility in Cancer Patients: Intracase Evaluation of Semen Quality.Journal of personalized medicine · 2023Article
- Digital Transformation in Toxicology: Improving Communication and Efficiency in Risk Assessment.ACS omega · 2023Review
- Genetic Variations of ferroportin-1(FPN1-8CG), TMPRSS6 (rs855791) and Hemojuvelin (I222N and G320V) Among a Cohort of Egyptian β-Thalassemia Major Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Association of Transferrin Gene Polymorphism with Cognitive Deficits and Psychiatric Symptoms in Patients with Chronic Schizophrenia.Journal of clinical medicine · 2022Article
- Iron deposition in multiple sclerosis: overall load or distribution alteration?European radiology experimental · 2022Article
- Common Single Nucleotide Polymorphism ofGenes · 2022Article
- Lack of association between C282Y and H63D polymorphisms in the hemochromatosis gene and risk of multiple sclerosis: A meta-analysis.Biomedical reports · 2022Article
- Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role ofFrontiers in genetics · 2022Article
- Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part I. Targeting a metabolic model rather than autoimmunity.Metabolic brain disease · 2021Review
- Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications.International journal of nanomedicine · 2021Review
- Deep Gray Matter Iron Content in Neuromyelitis Optica and Multiple Sclerosis.BioMed research international · 2020Article
- "International journal of molecular sciences · 2019Review
- Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing.Molecular genetics and metabolism reports · 2019Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIron 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.
methodsBy 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).
resultsThe 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).
conclusionsPolymorphisms 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.
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