Association Study Between VDR Gene Polymorphisms and Risk and Features of MG in Han Chinese Population

Study Overview
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Brief Summary
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The Vitamin D receptor gene (VDR) polymorphisms are the candidate genetic variants for susceptibility to autoimmune diseases. In the present study, the investigators aimed to assess the association between VDR polymorphisms and myasthenia gravis (MG) susceptibility and disease features in Chinese Han population.The patients with MG and healthy controls were genotyped for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms using the improved multiple ligase detection reaction. Information on age at onset, acetylcholine receptor antibody (AChR-Ab) and muscle-specific kinase antibody (MuSK-Ab) status, thymus status, involved muscles at onset and Osserman type at the maximum worsening during 2 years follow-up were obtained and used as the grouping basis of sub-classifications. Intergroup comparisons of allele and genotype frequencies, haplotype distributions were performed between MG group and the control group, and between each pair of MG subgroups.

Official Title
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Association Study Between Vitamin D Receptor Gene Polymorphisms and Risk and Features of Myasthenia Gravis in Han Chinese Population

Conditions
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Myasthenia Gravis, Ocular, Gene Polymorphism

Intervention / Treatment
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* Genetic: Genotype analysis for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of myasthenia gravis. Han Chinese population. Must be able to complete a 2-year follow-up visit. Exclusion Criteria: Clinical data collection can not be completed. Poor compliance.

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| MG group<br>Unrelated patients with MG were included in the study. They were enrolled in the Neurology Department of Beijing Tongren Hospital, Capital Medical University and fulfilled the clinical and electromyography diagnostic criteria for acquired MG. Simply, all MG patients met the following diagnostic criteria: typical symptoms of fluctuating muscle weakness, positive result of neostigmine test, and decremental response to low-frequency repetitive nerve stimulation. Information on age at onset, AChR / MuSK Abs status (partly), thymus status, involved muscles at onset and Osserman type at the maximum worsening during 2 years follow-up were obtained and used as the grouping basis of sub-classifications. They were genotyped for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms | Genetic: Genotype analysis for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms<br>* Genomic DNA was extracted from peripheral blood samples using a Wizard Genomic DNA Purification Kit (Promega, Madison,Wisconsin, USA) as per the product instruction. VDR (rs731236, rs1544410, rs7975232, rs2228570) polymorphisms were genotyped by the improved Multiple Ligase Detection Reaction (iMLDR) developed by Genesky Biotechnologies Inc. (Shanghai, China).<br>|
| Healthy control<br>The geography and ethnically matched control group consisted of 146 unrelated healthy subjects. They were genotyped for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms. | Genetic: Genotype analysis for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms<br>* Genomic DNA was extracted from peripheral blood samples using a Wizard Genomic DNA Purification Kit (Promega, Madison,Wisconsin, USA) as per the product instruction. VDR (rs731236, rs1544410, rs7975232, rs2228570) polymorphisms were genotyped by the improved Multiple Ligase Detection Reaction (iMLDR) developed by Genesky Biotechnologies Inc. (Shanghai, China).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between VDR gene polymorphism and MG susceptibility | Codominant, dominant and recessive genetic models and haplotype analysis were applied to compare the difference between MG and control groups. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of VDR gene polymorphism with MG subgroups | To study the precise effect of single nucleotide polymorphisms (SNPs) in the different population, the MG patients were divided into subgroups according to essential clinical variables, including onset age (≤50 or >50 years), thymus status (thymoma or non-thymoma, by pathology), AChR / MuSK Abs (positive or negative), onset involvement (ocular or generalized) and Osserman type at the maximum worsening (type I or IIa-IIb or III-V). The investigators analyzed the distribution of genes in each group. | up to 2 years |