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

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

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.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis, Ocular; Gene Polymorphism
• Intervention / Treatment: Genetic: Genotype analysis for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms

• Study Type: Observational
• Enrollment (Actual): 297

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tongren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed myasthenia gravis and healthy volunteers.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MG group; 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; 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).
Healthy control; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): May 9, 2022

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 15, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 15, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neuromuscular Diseases; Neurodegenerative Diseases; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: BeijingTH-20220509

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The IPD that support the findings of this study are available from the central contact person upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No