In The N am e O fG od D rAlsahebfosoul Im m unology D epartm ent Isfahan U niversity ofM edicalSciences
Onset most commonly between ages 20 and 40 Affects women about twice as often as men Statistics courtesy of the National MS Society.
Dec 23, 2015
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
In The Name Of God
Dr AlsahebfosoulImmunology Department Isfahan University of Medical Sciences
Onset most commonly between ages 20 and 40Affects 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 ) .
Uncommon among Turkmen ,Uzbeks , Kazakhs ,Chinese , African blacks
>2 million individuals are affected by MS disease worldwide.
Iran 20-60/100000Isfahan 73.4 / 100000
Isfahan is considered as an area with a medium to high risk of MS
EPIDEMIOLOGY
Caucasians are more at risk than other races
It costs approximately $ 35,000 per year for the treatment of 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.
ANNUAL COST
MS AS A COMPLEX DISEASE
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
Genome allelic variants
Single nucleotide polymor-phisms
Copy number variationInsertion-deletion polymor-
phismsDisease modifier genes
Disease susceptibility genes
Complex with multiple causal factors
Environmental agents Chemicals
UV light
Migration
Infectious agentsEBV, HHV-6, measles virus, HERV
Chlamydophila pneumonia . H.Pylori
Genetic predispositionHLA- DRB1*1501
HLA-DR2IL-2R and IL-7 receptor mutations
ETIOLOGY
Environmental factors
Latitude
SES
Migration
Infection
Vitamin D
Birth monthAs you increase latitude, mainly above and below 40° latitude, MS is more common in against latitude for sibling datathe 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 toIf 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 higher than in Iran
The viral infections may include chicken pox, measles,
or certain herpes.
Birthday in Spring
Hygiene Hypothesis
Reduction in MS release rate with increasing vitamin D
ENVIRONMENTAL FACTOR : VITAMIN D
Increase vitamin D
Decrease MS risk
MS :
ENVIRONMENT AND GENES
Geneticof
multiple sclerosis
Genetic Factor
Genome allelic variants
Sex
Racial group
Family history
women being affected 2–3 times more than men
women are in general more to have an Auto immune Disease.
Whites are more than twice as likely as other races to develop MS
African American men were shown to have an approximate 40% lower MS risk than white men
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%Monozygotic twins 30%
SNPs in HLA region as the strongest susceptibility loci for MS
FIGURE1
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
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)
EXAMPLES OF GENE DEFECTS
Gene Chro Function
IL2R 10 Regulation of T-cells
IL7R 5 Homeostasis of the memory T-cell pool
CD58 1Influences T-cell proliferation and differentiation
CLEC16A 16Provides signals for decisions between tolerance and immunity
CD226 18 Adhesion and co-stimulation T-cells
HLA-G 6 Regulating immune reactivity in the CNS
SOME MS RISK GENES OVERLAPPING WITH RISK GENESFOR OTHER AUTOIMMUNE DISEASES
Gene Chr Function Disease
IL7R α 5 Homeostasis of the memory T-cell pool
T1D
IL2R α 10 Regulation of T-cells T1D & Graves' disease
CLEC16A
16 Provides signals for decisions between tolerance and immunity Addison's disease
T1D
CD226 18 Adhesion and co-stimulation T-cells
T1D, RA, Graves‘ disease, Crohn's disease
CD58 1 Influences T-cell proliferation and differentiation
RA
Gene SNP Article title population year association
HLA-DRB1*1501 HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population
Iran 2010 Yes
CD40 rs6074022 Association of SNPs of CD40 Gene with Multiple Sclerosis in Russians
Russians 2013
Yes
rs1883832
NOTCH4(MHC Class III)
rs422951 SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients
Japanese 2012 Yes
HLA-DQA2(MHC Class II)
rs3997849
HLA-DRB1, HLA-DRB5 (MHC Class II)
rs660895
NRM (MHC Class I)
rs2269704
HLA-DQB1 rs1694112
CD6Non HLA
rs11230559
Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6
Spanish 2013 YES
rs2074225
rs650258
IL7R/CD58, CLEC16A/CTLA-4, and TYK2/IRF5
The influence of non-HLA gene polymorphisms and interactions on disease risk in aWestern Australian multiple sclerosis cohort
Australian 2013 Yes
Fok1 rs2228570 Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis
Spanish 2013 NO
Taq1 Rs731236
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
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
Non-MHC regions containing associated SNPs
Author Type of MS Country Year association
Shahbazi Iran 2010 Yes
Ghabaee Iran 2009 Yes
Kalanie RR & PP MS
Iran 2000 Yes
Amirzargar CPMS Iran 1998 NO
Elena García
Spain 2013 Yes
HLA-DRB1*1501 ALLELE & SUSCEPTIBILITY TO MS
Time until DRB1*1501 positive and negative* Expanded Disability Status Scale ( EDSS )
Association HLA DRB1*1501 & EDSS
Author place Year association
Kalanie Iran 2000 NO
Marrosu 2006 Yes
Marrosu Mediterraneanisland of Sardinia
1993 Low
Haegert Mediterraneanisland of Sardinia
1993 Low
HLA-DQA1*0102 ALLELE & SUSCEPTIBILITY TO MS
Author population Year associationKarin Weiner lachmi
Caucasian 2013 No
Olivier Andlauer Stanford 2012 No Ghabee Iran 2009 NO
Zivadinov northeastern Italy 2003 NO
Amirzargar Iran 1998 NO
Marrosu Southern European regions such as Sardinia
1993 NO
Marrosu Sardinia 1993 NO
Haegert Northeastern Italy 1993 NO
HLA-DQB1*0602 ALLELE & SUSCEPTIBILITY TO MS
can post-transcriptionally regulate entire sets of genes
are involved in regulation of the immune system and in the generation of T regulatory cells
MICRO RNA
2-∆∆C
t
2-∆∆C
t
All miRNAs in the network are upregulated in MS patiens
Cell 2009
microRNA
Gene Title Article Population year
miRNA MicroRNAs and multiple sclerosis: from physiopathology toward therapy
Zare Iran 2013
micro-RNAs (miR-338, miR-155 and miR-491)
Impaired neurosteroid synthesis in multiple sclerosis
Noorbakhsh Iran 2011
IL-17A mRNA Interleukin-17A and interleukin-17F mRNA expression in peripheral blood mononuclear cells of patients with multiple sclerosis.
Babaloo Iran 2010
miRNA MicroRNAs as Diagnostic and Therapeutic Targets in Multiple Sclerosis
Pahlevan Kakhki
Iran 2013
miRNA MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47.
Junker A German 2009
miRNA (miR-614, miR-572, miR-648, miR-1826, miR-422a and miR-22)
Circulating microRNAs involved in multiple sclerosis.
Siegel SR USA 2012
hsa-miR-145 Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls
Keller A South Africa
2009
MS ARTICLE:
IRAN , ISFAHAN& OTHER STATE
Gene Title Article Population year
INF beta-1a Neutralizing antibodies in multiple sclerosis patients on weekly intramuscular Avonex and biosimilar interferon beta-1a (CinnoVex): comparing results of measurements in two different laboratories
Shahkarami Isfahan, Iran 2013
Apo E Polymorphism of Apo lipoprotein E gene and the risk of MS
Sadeghi Isfahan, Iran 2013
VDR What is the Real Fate of Vitamin D in Multiple Sclerosis?
Shaygannejad Isfahan, Iran 2013
Chlamydia Pneumonia
In CSF
Detection of Chlamydia Pneumoniae in the Cerebrospinal Fluid of Multiple Sclerosis Patients and other Neurological Disorders
Etemadifar Isfahan, Iran 2012
CD24 CD24 gene allele variation is not associated with oligoclonal IgG bands and IgG index of multiple sclerosis patients.
Saadatnia Isfahan, Iran 2012
MS & Guillain-Barre Linkage of Multiple Sclerosis and Guillain-Barre Syndrome: A Population-Based Survey in Isfahan, Iran
Etemadifar Isfahan, Iran 2012
Epilepsy & MS Epileptic seizures in early-onset multiple sclerosis: a population-based study in Isfahan, Iran.
Roomizadeh Isfahan, Iran 2011
Ndufv2 investigation of relationship between Ndufv2 gene and multiple sclerosis disease
Akbari chelar Isfahan, Iran 2011
Gene Title Article Population year
Female /Male Increasing female preponderance of multiple sclerosis in Isfahan, Iran: a population-based study.
Maghzi Isfahan, Iran 2010
HLA-DRB1 Characterization of D6S2806 and D6S2879 short tandem repeat loci in HLA-DRB1 region in Iranian population
Vallian Isfahan, Iran 2010
CD14,CD4,CD8 multiple sclerosis center,tel has homer :laquinimiod suppress antigen presentation in RRMS :in vitro high-throughput gene expression study
shaygannejad Isfahan, Iran 2010
EBV genotypes Viral pathophysiology of multiple sclerosis: A role for Epstein-Barr virus infection?
Etemadifar Isfahan, Iran 2010
CD24 CD24 gene polymorphism is associated with the disease progression and susceptibility to multiple sclerosis in the Iranian population.
Etemadifar Isfahan, Iran 2009
Gene Title Article Population Year
RETN resistin(Rs1862513)
A polymorphism in the resistin gene promoter and the risk of multiple sclerosis.
Hossein-Nezhad
Iran 2013
RAR Impact of Vitamin A Supplementation on RAR Gene Expression in Multiple Sclerosis Patients.
Bitarafan Iran 2013
cytochrome c oxidase (COX)
Investigation of cytocrom c oxidase gene subunits expression on the Multiple sclerosis
Safavizadeh Iran 2013
CXCR1 & CXCR2
Quantitative evaluation of CXCL8 and its receptors (CXCR1 and CXCR2) gene expression in Iranian patients with MS
Almasi Iran 2013
IL2 The association of -475 and -631 interleukin-2 gene polymorphism with multiple sclerosis in Iranian patients
Sayad Iran 2013
MBP/PLP Regional regulation of glutamate signaling during cuprizone-induced demyelination in the brain.
Azami Tameh Iran 2013
mitochondrial gene Multiple sclerosis and mitochondrial gene variations: a review Andalib Iran 2013
IL-6 Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells
Mohyeddin Bonab
Iran 2013
Gene Title Article Population year
NF-κB1 Relationship between NF-κB1 -94 ins/del ATTG polymorphism and susceptibility of multiple sclerosis in Iranian MS patients
Zahednasab Iran 2013
CCR5 Is the CCR5 Δ 32 mutation associated with immune system-related diseases?
Ghorban Iran 2013
IL-10 Is the IL-10 promoter polymorphism at position -592 associated with immune system-related diseases?
Karimabad Iran 2013
(HHV6) sequence Monitoring of Active Human Herpes Virus 6 Infection in Iranian Patients with Different Subtypes of Multiple Sclerosis
Ramroodi Iran 2013
APOE Apolipoprotein E polymorphisms status in Iranian patients with MS
Rafiei Iran 2012
human caveolin 1 (CAV1)
Haplotypes across the human CAV1 gene upstream purine complex significantly alter gene expression: implication in neurodegenerative disorders.
Heidari Iran 2012
HLA-DRB1 and HLA-DQB1
The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk and severity in Iranian patients with multiple sclerosis.
Kollaee Iran 2012
IL-4 Association of interleukin-4 polymorphisms with multiple sclerosis in southeastern Iranian patients.
Arababadi Iran 2012
CD94,CD178 and TRAIL
Evaluation of apoptosis-related genes: Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients.
Mohamadzadeh Iran 2012
Gene Title Article Population
year
CXC chemokine SDF-1α (CXCL12)
The SDF-1 3'a genetic variation of the chemokine SDF-1α (CXCL12) in parallel with its increased circulating levels is associated with susceptibility to MS: a study on Iranian multiple sclerosis patients.
Azin IRAN 2012
CCR2 and CCR5 Ccr2-64i and Ccr5 Δ32 Polymorphisms in Patients with Late-Onset Alzheimer’s disease; A Study from Iran (Ccr2-64i And Ccr5 Δ32 Polymorphisms in Alzheimer’s disease)
IRAN 2012
CD24 Investigation of CD24 and its expression in Iranian relapsing-remitting MS
Kollaee IRAN 2011
MICB MICB gene expression on peripheral blood mononuclear cells and susceptibility to multiple sclerosis in north of Iran.
Abediankenari IRAN 2011
CAV1 The human caveolin 1 gene upstream purine complex and neurodegeneration--a common signature.
Heidari IRAN 2011
Olig2, MBP, Nogo-A and GFAP mRNAs
Castration attenuates myelin repair following lysolecithin induced demyelination in rat optic chiasm: an evaluation using visual evoked potential, marker genes expression and myelin staining.
Sherafat IRAN 2011
paraoxonase 1 (PON1)
Lack of association between paraoxonase 1 Q192R polymorphism and multiple sclerosis in relapse phase: A case-control study.
Moghtaderi IRAN 2011
FOXP3 FOXP3 gene expression in multiple sclerosis patients pre- and post mesenchymal stem cell therapy.
Mohajeri IRAN 2011
Gene Title Article Population year
HLA-DRB1*1501 and TNF-alpha
Interaction of HLA-DRB1*1501 allele and TNF-alpha -308 G/A single nucleotide polymorphism in the susceptibility to multiple sclerosis.
Shahbazi IRAN 2011
IL7Ra Variation in SNPs of the IL7Ra gene is associated with multiple sclerosis in the Iranian population.
Heidari IRAN 2011
CXCR3, CCR5 and CCR6
Expression of chemokine receptors on Th1/Th2 CD4+ lymphocytes in patients with multiple sclerosis.
Andalib IRAN 2011
Epidemiology of Multiple sclerosis in Mashhad
Mostafavian IRAN 2011
HLA-DRB1*15 HLA allele frequencies in Iranian multiple sclerosis patients
Amini IRAN 2011
IL7Ra Association and Expression Study of IL7Ra Gene Polymorphisms In Iranian Multiple Sclerosis Patients
Javadian IRAN 2011
Polymorphism of Apo lipoprotein E and Angiotensin converting enzyme genes and the risk of multiple sclerosis.
Mousavian IRAN 2011
COX5B Investigation of Relationship Between COX5B Gene Expression and Multiple Sclerosis Disease
Motaei IRAN 2011
microRNA(miR-338,miR-155 & miR491)
Impaired neurosteroid synthesis in multiple sclerosis Noorbakhsh IRAN 2011
Gene Title Article Population year
IL-17A and IL-17F Interleukin-17A and interleukin-17F mRNA expression in peripheral blood mononuclear cells of patients with multiple sclerosis.
Babaloo IRAN 2010
CTLA-4 CTLA-4 gene polymorphisms (-318C/T, +49A/G, +6230A/G) in Iranian patients with multiple sclerosis.
Heidari IRAN 2010
non-HLA The role of non-HLA single nucleotide polymorphisms in MS susceptibility.
Bahreini IRAN 2010
HLA-DRB1*1501 allele and IL-2
High frequency of the IL-2 -330 T/HLA-DRB1*1501 haplotype in patients with multiple sclerosis
Shahbazi IRAN 2010
TNFa & TGF-b & IL6 & IL10
Cytokines genes polymorphisms and risk of multiple sclerosis.
Izad IRAN 2010
Foxp3 Effect of IFN-beta therapy on the frequency and function of CD4(+)CD25(+) regulatory T cells and Foxp3 gene expression in relapsing-remitting multiple sclerosis (RRMS): a preliminary study.
Namdar IRAN 2010
human CAV1 Skew in the human caveolin 1 gene upstream purine complex homozygote haplotype compartment in multiple sclerosis.
Yeganeh IRAN 2009
CTLA4 CTLA4 exon 1 and promoter polymorphisms in patients with MS
Yousefipour IRAN 2009
IL-2, IFN-g, and IL-12
IL-2, IFN-gamma, and IL-12 gene polymorphisms and susceptibility to multiple sclerosis.
Shokrgozar IRAN 2009
Gene Title Article Population
year
CCR5-delta CCR5-delta 32 allele is associated with the risk of developing multiple sclerosis in the Iranian population.
Shahbazi IRAN 2009
HLA-DRB, DQA and DQB
Optic neuritis, multiple sclerosis and HLA: results of a 4-year follow-up study
Amirzargar IRAN 2005
IFN- gamma Interferon-gamma gene polymorphism in Iranian patients with MS
Izad IRAN 2004
mitochondrial DNA (mtDNA)
Lack of association between Leber's hereditary optic neuropathy primary point mutations and multiple sclerosis in Iran.
Houshmand IRAN 2004
HLA class II (DRB1, DQA1 and DQB1)
HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients
Amirzargar IRAN 1998
Apolipoprotein E (apoE)
Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts.
Barzegar IRAN 2008
CTLA4 exon 1 CTLA-4 exon 1 A/G polymorphism in Iranian patients with multiple sclerosis.
Borhani IRAN 2008
IL-1, IL-1R and TNFa IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis.
Sarial IRAN 2008
mitochondrial tRNA Investigation on mitochondrial tRNA(Leu/Lys), NDI and ATPase 6/8 in Iranian multiple sclerosis patients
Ahari IRAN 2007
Gene Title Article Population year
TNF-alpha TNF-alpha, TNF-beta and IL-4 gene polymorphisms in Iranian patients with multiple sclerosis.
Kamali IRAN 2007
ICAM-1 Intercellular adhesion molecule-1 gene polymorphism in Iranian patients with multiple sclerosis.
Mousavi IRAN 2007
IL-2,IL-6,TNF-alpha
Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients.
Amirzargar IRAN 2007
Fcg RIIA & Fcg RIIIA Investigation of Fcg RIIA and Fcg RIIIA Polymorphism in Multiple Sclerosis: A Case Control Study
Nikseresht IRAN 2006
IL-8 and CXCR2 IL-8 (-251 A/T) and CXCR2 (+1208 C/T) gene polymorphisms and risk of multiple sclerosis in Iranian patients.
Kamali IRAN 2006
mitochondrial genome Mitochondrial D-loop variation in Persian multiple sclerosis patients: K and A haplogroups as a risk factor
Hassani IRAN 2006
Thank you so Much For Your Attention
Related Documents
