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Multiple Sclerosis

Multiple Sclerosis. Onset most commonly between ages 20 and 40 Affects women about twice as often as men Statistics courtesy of the National MS Society. Prevalence. In northern Europe ,Scandinavia , British island, North America (about 1-2 in 1000 ) .

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Multiple Sclerosis

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  1. Multiple Sclerosis • Onset most commonly between ages 20 and 40 • Affects women about twice as often as men Statistics courtesy of the National MS Society

  2. Prevalence • In northern Europe ,Scandinavia ,British island, North America (about 1-2 in1000 ) . • Uncommon among Turkmen ,Uzbeks , Kazakhs ,Chinese , African blacks

  3. Epidemiology • >2 million individuals are affected by MS disease worldwide. • Iran 20-60/100000 • Isfahan 73.4/100000 • Isfahan is considered as an area with a medium to high • riskof MS • Caucasians are more at risk than other races

  4. Annual Cost • It costs approximately $35,000 per year for the treatmentof MS. • The individual costs of RR drugs (per year): Novantrone* - $5,000 - $10,000 Copaxone – $16,000 Avonex & Betaseron - $19,000 Rebif - $23,000 • In a lifetime, someone with MS will likely pay $3.2 million in treatment costs.

  5. Environment Pathogens Chemicals Smoking Diet Sun exposure Vitamin D Epigenetic, Post-genomic And regulatory events Gene rearrangements Somatic mutations Messenger RNA splicing And/or editing Retroviral sequences Methylation MicroRNAs MS AS a complex disease Genome allelic variants Single nucleotide polymorphisms Copy number variation Insertion-deletion polymorphisms Disease modifier genes Disease susceptibility genes

  6. ETIOLOGY • Complex with multiple causal factors • Environmental agents • Chemicals • UV light • Migration • Infectious agents • EBV, HHV-6, measles virus, HERV • Chlamydophila pneumonia . H.Pylori • Genetic predisposition • HLA- DRB1*1501 • HLA-DR2 • IL-2R and IL-7 receptor mutations

  7. As you increase latitude, mainly above and below 40° latitude, MS is more common in against latitude for sibling data the prevalence of MS in low-risk regions in areas nearer the equator is increasing(South America and Spain) Your socioeconomic status can also affect the occurrence of MS If you move before the age of 15, your risk is that of the people in the country you move to If you move after the age of 15,your risk stays fixed at that of the country you grew up in. The MS risk in the Iranian migrants in Gothenburg was several times higherthan in Iran Reduction in MS release rate with increasing vitamin D The viral infections may include chicken pox, measles, or certain herpes. Hygiene Hypothesis Birthday in Spring

  8. Environmental factor : vitamin D Increase vitamin D Decrease MS risk

  9. MS :environment and Genes

  10. Genetic of multiple sclerosis

  11. SNPs in HLA region as the strongest susceptibility loci for MS women are in general more to have an Auto immune Disease. women being affected 2–3 times more than men African American men were shown to have an approximate 40% lower MS risk than white men Whites are more than twice as likely as other races to develop MS a normal population 0.1% parent, brothers, or sisters 3% second-degree relative 0.1% both of your parents 20% Half siblings 1.5% full siblings 3-4% Monozygotictwins 30%

  12. figure1

  13. Its cause may be genetic or of environmental origin (infectious) MHC genes in chromosome six, particularly DR15 and DQ6 alleles More common in people living further from the equator It is an inflammatory disease with an auto-immune basis Blood-brain barrier not permeable unless triggered by a virus

  14. EXAMPLES OF GENE DEFECTS • 57 candidates genes with risk factors • MHC II (HLA-DR:DRB1*1501 ) • non-MHC genes(IL2Ra , IL7Ra) • AIRE-1 (autoimmune regulator-1 gene) mutation (usually deletion) • Epistasis (interaction of susceptibility genes)

  15. Some MS risk genes overlapping with risk genesfor otherautoimmune diseases

  16. Overview of published genome‑wide association studies in MS Oksenberg, J. R. & Baranzini, S. E.(2010) Multiple sclerosis genetics—is the glass half full, or half empty? Nat. Rev. Neurol. doi:10.1038/nrneurol.2010.91

  17. Established non‑MHC susceptibility genes and variants in MS Oksenberg, J. R. & Baranzini, S. E.(2010) Multiple sclerosis genetics—is the glass half full, or half empty? Nat. Rev. Neurol. doi:10.1038/nrneurol.2010.91

  18. Non-MHC regions containing associated SNPs

  19. HLA-DRB1*1501 allele & Susceptibility to MS

  20. Association HLA DRB1*1501 & EDSS Time until DRB1*1501 positive and negative * Expanded Disability Status Scale ( EDSS )

  21. HLA-DQA1*0102allele & Susceptibility to MS

  22. HLA-DQB1*0602allele & Susceptibility to MS

  23. Micro RNA • can post-transcriptionally regulate • entire sets of genes • are involved in regulation of the • immune system and in the • generation of T regulatory cells

  24. All miRNAs in the network are upregulated in MS patiens 2-∆∆Ct 2-∆∆Ct Cell 2009

  25. microRNA

  26. Ms Article: Iran , Isfahan & other state

  27. Thank you so Much For Your Attention

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