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[Title] HLA-DRB1*14 is a protective allele for multiple sclerosis in an admixed Colombian population.

OBJECTIVE: The aim of this study was to determine ancestry informative markers, mitochondrial DNA haplogroups, and the association between HLA-DRB1 alleles and multiple sclerosis (MS) in a group of patients from Bogotá, Colombia.

To test the association of HLA polymorphisms and MS, we ran separate multivariate logistic regression models.

Bonferroni correction was used to account for multiple regression tests.

RESULTS: A total of 100 patients with MS (mean age 40.4 ± 12 years; 70% females) and 200 healthy controls (mean age 37.6 ± 11 years; 83.5% females) were included in the analysis.

In the multivariate model, HLA-DRB1*15 was significantly associated with MS (odds ratio [OR] = 3.05, p < 0.001), whereas HLA-DRB1*14 was confirmed as a protective factor in our population (OR = 0.16, p = 0.001).

CONCLUSIONS: This study provides evidence indicating that HLA-DRB1*15 allele confers susceptibility to MS and HLA-DRB1*14 allele exerts resistance to MS in a highly admixed population.

This latter finding could partially explain the low prevalence of MS in Bogotá, Colombia.

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(PMID = 26740965.001).

[ISSN] 2332-7812

[Journal-full-title] Neurology® neuroimmunology & neuroinflammation

[ISO-abbreviation] Neurol Neuroimmunol Neuroinflamm

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Other-IDs] NLM/ PMC4694072

   

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[Title] An evaluation of tumor necrosis factor microsatellite alleles in genetic susceptibility to multiple sclerosis.

We have analyzed the distribution of tumor necrosis factor (TNF) a and -b microsatellite alleles in HLA-DQ and -DR typed Swedish patients with multiple sclerosis (MS) (n = 122) and ethnically matched control subjects (n = 178).

TNFaII was significantly associated with MS.

However, TNFaII (alone or in combination with TNFb4) did not show any disease association independent of DQA1*0102/ DQB1*0602/DR2, whereas the previously reported strong association with HLA-DQA1*0102/DQB1*0602/DR2 in Scandinavian populations was confirmed.

Therefore the association of TNFaII (and TNFb4) is most likely secondary to the increase of DQA1*0102/DQB1*0602/DR2 in MS patients.

The proportion of TNFa6 positive individuals was lower among DR2-negative MS patients than among DR2-negative controls (P = 0.08).

Since the presence of the TNFa6 allele correlates with low TNF alpha production in response to lipopolysaccharide, it could be speculated that DR2-negative MS patients have an increased risk of being high TNF alpha producers in response to exogenous stimuli.

[MeSH-major] Multiple Sclerosis / epidemiology. Multiple Sclerosis / genetics. Tumor Necrosis Factor-alpha / genetics

[MeSH-minor] Alleles. Evaluation Studies as Topic. Gene Frequency. Genetic Predisposition to Disease. HLA-DQ Antigens / genetics. HLA-DQ Antigens / immunology. HLA-DQ alpha-Chains. HLA-DQ beta-Chains. HLA-DR2 Antigen / genetics. HLA-DR2 Antigen / immunology. Humans. Lymphotoxin-alpha / classification. Lymphotoxin-alpha / genetics. Microsatellite Repeats / genetics. Sweden / epidemiology

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(PMID = 9345451.001).

[ISSN] 1352-4585

[Journal-full-title] Multiple sclerosis (Houndmills, Basingstoke, England)

[ISO-abbreviation] Mult. Scler.

[Language] eng

[Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / HLA-DQ Antigens; 0 / HLA-DQ alpha-Chains; 0 / HLA-DQ beta-Chains; 0 / HLA-DQA1 antigen; 0 / HLA-DQbeta antigen; 0 / HLA-DR2 Antigen; 0 / Lymphotoxin-alpha; 0 / Tumor Necrosis Factor-alpha

   

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[Title] Genetic association of rs1520333 G/A polymorphism in the IL7 gene with multiple sclerosis susceptibility in Isfahan population.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory neurodegenerative disease in which the insulating membrane of central nervous system is damaged.

The etiology of MS includes both genetic and environmental causes.

A Genome - Wide Association Study (GWAS) recognized genetic single nucleotide polymorphisms (SNP) linked with MS predisposition among which immunologically related genes are considerably over signified.

The purpose of the present study is to explore the association of rs1520333 C/T polymorphism in the IL7 gene variants with the risk of MS in a subset of Iranian population.

MATERIALS AND METHODS: In this case - control study, 110 cases with MS and 110 controls were contributed.

RESULT: We demonstrated the important association between G allele [odds ratio (OR) =1.6614, confidence interval (CI) =1.12-2.47, P = 0.0124] and GG genotype (OR = 7.45, 95% CI = 2.13-25.97, P 0.0016) of the rs1520333 SNP for susceptibility to MS after adjustment for age, and gender.

OR adjusted for age, gender, and body mass index has displayed similar outcomes.

CONCLUSION: These results indicate that the rs1520333 SNP is a significant susceptibility gene variant for development of MS in the Iranian population.

Nevertheless, functional studies are required to completely elucidate how this SNP contributed to MS pathogenesis.

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(PMID = 25538924.001).

[ISSN] 2277-9175

[Journal-full-title] Advanced biomedical research

[ISO-abbreviation] Adv Biomed Res

[Language] eng

[Publication-type] Journal Article

[Publication-country] India

[Other-IDs] NLM/ PMC4260277

[Keywords] NOTNLM ; GWAS / IL7 gene / multiple sclerosis / polymorphism

   

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[Title] Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis.

BACKGROUND: The association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial.

METHODS: This meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS.

Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models.

RESULTS: A total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis.

The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype.

High latitude (40.1-50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively).

Additionally, Asian or low latitude (20.1-30°N) people with ApaI homozygous genotype, '> 2013' publication year people in the allele contrast and dominant models of FokI, '> 40 years' age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk.

CONCLUSION: TaqI polymorphism is a significant protective factor for MS.

However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.

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[Copyright] Copyright © 2017 Elsevier Ltd. All rights reserved.

(PMID = 28780323.001).

[ISSN] 1096-1208

[Journal-full-title] Microbial pathogenesis

[ISO-abbreviation] Microb. Pathog.

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

[Keywords] NOTNLM ; ApaI / BsmI / FokI / Meta-analysis / Multiple sclerosis / TaqI

   

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[Title] [The relation between the HLA-DRB1*1501 allele and the severity of multiple sclerosis in a sample of the Spanish population from the Balearic Islands: the influence exerted by sex].

[Transliterated title] Relación entre el alelo HLA-DRB1*1501 y la gravedad de la esclerosis múltiple en una muestra de población española perteneciente a las Islas Baleares: influencia del sexo.

INTRODUCTION: There is some controversy about the possible relation between HLA-DR2 (DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602) and the severity of multiple sclerosis (MS), which could be due, at least in part, to methodological differences among the different studies dealing with this subject and/or to a lack of phenotypic homogeneity within the series of patients.

AIMS: This study aims to contribute information about the possible relation between DR2 (more specifically the HLA-DRB1*1501 allele) and the severity of MS.

PATIENTS AND METHODS: We conducted a study of 43 individuals with clinically defined MS, whose degree of severity was determined using Kurtzke's EDSS, and 107 controls from a similar ethnic origin.

STATISTICS: Chi2 test, Mann-Whitney test and Kendall correlation coefficient.

RESULTS: DRB1*1501 is associated with the presence of MS only in females and with lower severity of the disease only in males.

CONCLUSIONS: The absence of a relation between DRB1*1501 and the severity of MS reported in many studies could be due to not stratifying the patients according to sex.

[MeSH-major] HLA-DR Antigens / genetics. Multiple Sclerosis / genetics

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(PMID = 14752708.001).

[ISSN] 0210-0010

[Journal-full-title] Revista de neurologia

[ISO-abbreviation] Rev Neurol

[Language] spa

[Publication-type] English Abstract; Journal Article

[Publication-country] Spain

[Chemical-registry-number] 0 / HLA-DR Antigens; 0 / HLA-DRB1 Chains

   

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[Title] Modulation of IFNAR1 mRNA expression in multiple sclerosis patients.

Real-Time PCR analysis of mRNA for all IFNAR components in multiple sclerosis patients naïve for therapy and undergoing long-term treatment with interferon-beta shows that IFNAR1 mRNA level is lower than in healthy controls.

Since chronic cell stimulation by interferon-beta induces IFNAR protein down-regulation, we suggest that the increase of IFNAR1 mRNA might serve as a mechanism for counterbalancing the loss of protein receptor, enhancing, at least in this sub-group of patients, cell responsiveness to interferon-beta.

[MeSH-major] Multiple Sclerosis, Chronic Progressive / immunology. Multiple Sclerosis, Chronic Progressive / metabolism. Multiple Sclerosis, Relapsing-Remitting / immunology. Multiple Sclerosis, Relapsing-Remitting / metabolism. RNA, Messenger / biosynthesis. Receptor, Interferon alpha-beta / biosynthesis. Receptor, Interferon alpha-beta / genetics

[MeSH-minor] Adult. Female. GTP-Binding Proteins / analysis. GTP-Binding Proteins / biosynthesis. Humans. Interferon-beta / therapeutic use. Male. Myxovirus Resistance Proteins. Orthomyxoviridae / immunology. Protein Isoforms / biosynthesis. Protein Isoforms / genetics

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(PMID = 18482773.001).

[ISSN] 0165-5728

[Journal-full-title] Journal of neuroimmunology

[ISO-abbreviation] J. Neuroimmunol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] Netherlands

[Chemical-registry-number] 0 / IFNAR1 protein, human; 0 / IFNAR2 protein, human; 0 / Myxovirus Resistance Proteins; 0 / Protein Isoforms; 0 / RNA, Messenger; 156986-95-7 / Receptor, Interferon alpha-beta; 77238-31-4 / Interferon-beta; EC 3.6.1.- / GTP-Binding Proteins

   

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[Title] Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis.

The potential relevance of chromosome 7q21-22 in susceptibility to multiple sclerosis (MS) has been highlighted in genome-wide linkage screens as well as in association studies of 7q-specific polymorphic microsatellites.

Especially, recent, independently performed studies have provided evidence for significant association of the markers D7S554 and D7S3126 with MS in Sardinian, Northern Irish and Spanish-American cohorts.

The gene most closely located to these markers is the neuropeptide preprotachykinin-1 (TAC1) gene.

Both its position and the array of biological functions exerted by its expression products make it a logical primary choice for further scrutiny as the putative chromosome 7q21-22 MS susceptibility gene.

We report identification of eight polymorphisms in this gene by means of a sequencing approach.

One of these, an intron 1 single-nucleotide polymorphism (SNP), showed significant association with MS (P=0.009).

Two-marker haplotypes composed of allelic combinations of TAC1 promoter-intron 1 SNPs were highly significantly associated with MS and more so with the relapsing-remitting form of this disease.

While independent reproduction of these data in other data sets is indicated, our work is suggestive for a role of the TAC1 gene in MS.

Genes and Immunity (2005) 6, 265-270. doi:10.1038/sj.gene.6364175 Published online 24 February 2005.

[MeSH-major] Multiple Sclerosis / genetics. Protein Precursors / genetics. Tachykinins / genetics

[MeSH-minor] Genetic Predisposition to Disease. Haplotypes. Humans. Introns. Models, Genetic. Multiple Sclerosis, Relapsing-Remitting / genetics. Promoter Regions, Genetic

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(PMID = 15729363.001).

[ISSN] 1466-4879

[Journal-full-title] Genes and immunity

[ISO-abbreviation] Genes Immun.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Protein Precursors; 0 / Tachykinins; 0 / preprotachykinin

   

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[Title] Platelet-activating factor acetylhydrolase gene polymorphism and its activity in Japanese patients with multiple sclerosis.

We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G(994)-->T) and PAF-AH activity with susceptibility and severity of multiple sclerosis (MS) in Japanese.

DNA was collected from 216 patients with clinically definite MS (65 opticospinal MS (OS-MS) and 151 conventional MS (C-MS)) and from 213 healthy controls.

No statistically significant difference in the frequency of genotypes and alleles of the plasma PAF-AH polymorphism was observed among OS-MS patients, C-MS patients and healthy controls.

However, the missense mutation tended to be associated with the severity of OS-MS, especially in females (GT/TT genotypes; 51.7% in female rapidly progressive OS-MS vs. 26.6% in female controls, p=0.0870).

Moreover, PAF-AH activities were significantly lower in MS than in controls, irrespective of clinical subtypes, among those carrying the identical polymorphism in terms of nucleotide position 994 of the PAF-AH gene.

These findings suggest that the PAF-AH gene missense mutation has no relation to either susceptibility or severity of C-MS, yet its activity is down-regulated, and that the mutation has no relation with susceptibility of OS-MS, yet it may confer the severity of female OS-MS.

[MeSH-major] 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics. 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism. Multiple Sclerosis / enzymology. Multiple Sclerosis / genetics. Polymorphism, Genetic

[MeSH-minor] Adult. Alleles. Asian Continental Ancestry Group. Enzyme Activation / genetics. Female. Gene Frequency. Gene Silencing. Genotype. Humans. Male. Middle Aged. Mutation, Missense. Neuromyelitis Optica / enzymology. Neuromyelitis Optica / genetics. Severity of Illness Index

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(PMID = 15081260.001).

[ISSN] 0165-5728

[Journal-full-title] Journal of neuroimmunology

[ISO-abbreviation] J. Neuroimmunol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Netherlands

[Chemical-registry-number] EC 3.1.1.47 / 1-Alkyl-2-acetylglycerophosphocholine Esterase

   

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[Title] [Detection of viral genomes of the Herpesviridae family in multiple sclerosis patients by means of the polymerase chain reaction (PCR)].

[Transliterated title] Determinación de genomas de virus de la familia Herpesviridae en enfermos de esclerosis múltiple, por la reacción en cadena de la polimerasa (PCR).

BACKGROUND: The multiple sclerosis seems to be the junction between genetics alteration and an unknown environmental factor, that they would originate an autoimmune alteration, that they would be the reason of the inflammation and demyelinization responsible of the disease.

MATERIALS AND METHODS: 204 blood samples were studied: 102 from relapsing-remitting multiple sclerosis patients (43 were undergoing beta-interferon treatment), and 102 from blood donors with the same age and sex than multiple sclerosis patients.

RESULTS: a) we only found significative difference (p = 0.0001) in HHV-6: 21.5% donors positive samples (22/102), opposite to 49.02% of positivity in mulytiple sclerosis patients (50/102);.

CONCLUSIONS: Our results suggest us that HHV-6 can play an important role in the multiple sclerosis development.

[MeSH-major] DNA, Viral / blood. Genome, Viral. Herpesviridae / isolation & purification. Herpesviridae Infections / epidemiology. Multiple Sclerosis / virology. Polymerase Chain Reaction. Viremia / virology

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(PMID = 10974766.001).

[ISSN] 0213-005X

[Journal-full-title] Enfermedades infecciosas y microbiología clínica

[ISO-abbreviation] Enferm. Infecc. Microbiol. Clin.

[Language] spa

[Publication-type] English Abstract; Journal Article

[Publication-country] SPAIN

[Chemical-registry-number] 0 / Antiviral Agents; 0 / DNA, Viral; 77238-31-4 / Interferon-beta