Polymorphisms of Interleukins, Glypican, and Human Leukocyte Antigen Genes and Treatment Response in Multiple Sclerosis.

Study Overview
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Brief Summary
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HLA-DRB1 * Gene and some genes involved in inflammation and immunity (IL-7R, GPC5, CTSS) have been linked to risk of MS and the response to treatment with immunomodulators. This research aims to estimate the risk that confers some variations in the sequence of these genes.

Detailed Description
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Genes HLA-DRB1 * and some genes involved in inflammation and immunity have been linked to risk of MS and the response to treatment with immunomodulators. The HLA-DRB1 * genes have been associated with risk and response to treatment in MS in multiple studies; however, other genes have been controversial. This research aims to estimate the risk for MS that confers some variations in the sequence of IL-7R, GPC5, CTSS, HLA-DRB1 genes. Furthermore, it seeks to determine whether these gene variants (polymorphisms) are associated with treatment response to immunomodulators. Subjects with MS and healthy subjects will be taken to assess the risk for MS. Besides the investigators obtain the medical history of relapse to assess response to treatment in accordance with Expanded Disability Status Scale (EDSS) and relapses.

Official Title
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Association of Polymorphisms of the Interleukin-7 Receptor-α (IL-7R), Glypican 5 (GPC5), Interleukin-2 Receptor-α (IL2-RA) , Human Leukocyte Antigen Class II Beta Chain (HLA-DRB1) Genes and Treatment Response in Multiple Sclerosis (MS).

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Cases: Subjects with multiple sclerosis 18 and over EDSS less than 5 Signed informed consent Inclusion Criteria for Controls: Healthy subjects 18 and over Signed informed consent Exclusion Criteria for Cases: Mental retardation Withdrawal of consent No immunomodulatory treatment Exclusion Criteria for Controls: Mental retardation Withdrawal of consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Subjects with Relapsing-Remitting Multiple Sclerosis. Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined. | Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.<br>* The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.<br>|
| Controls<br>Healthy subjects. Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined. | Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.<br>* The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.<br>|
| Responders<br>Subjects with MS treated for at least two years that have less than one relapse per year or who had an increase of <1.5 points on the Expanded Disability Status Scale (EDSS) (if baseline EDSS was 0) or no increase in EDSS (baseline EDSS ≥1). Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined. | Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.<br>* The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.<br>|
| No responders<br>Subjects with MS that have more than one relapse per year treated for at least two years, and who had ≥1 relapse(s) or an increase of 1.5 points on the EDSS (if baseline EDSS was 0) or an increase of ≥0.5 points (baseline EDSS ≥1). Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined. | Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.<br>* The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response evaluated by relapses per year, evaluated during two years after recruitment. | Treatment response evaluated by relapses per year during two years after recruitment. The relapses are defined by any neurological sign or symptom that happens at least 30 days after any previous neurological deterioration episode began. | Two Years | 
| Treatment response evaluated by Expanded Disability Status Scale (EDSS) during two years after recruitment. | Treatment response evaluated by Expanded Disability Status Scale (EDSS) during two years after recruitment. The EDSS scale ranges from 0 to 10; the increments are in 0.5. Scoring is based on an examination by a neurologist about the level of disability. | Two Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Risk Conferred by Single Nucleotide Polymorphisms (SNPs) of Interleukins, Glypican, and Human Leukocyte Antigen Genes. | The risk conferred by SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes: calculated by odds ratio when the allele frequencies of SNPs cases are compared with the allele frequencies of SNPs in healthy subjects. | One Year |