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BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder.

Bo-Wen Yin1,2,3, Bin Li1,2, Arshad Mehmood1,2

  • 1Department of Neurology, The Second Hospital of Hebei Medical University, City Shijiazhuang, Province Hebei, China.

CNS Neuroscience & Therapeutics
|October 12, 2021
PubMed
Summary

The B-lymphoid tyrosine kinase (BLK) rs2248932 G allele may protect against neuromyelitis optica spectrum disorder (NMOSD) in Chinese Han individuals. BLK gene expression is lower in NMOSD patients but higher in acute, untreated cases.

Keywords:
B-lymphoid tyrosine kinasemRNAneuromyelitis optica spectrum disorderrs2248932single nucleotide polymorphisms

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Area of Science:

  • Genetics and Immunology
  • Neuroscience
  • Autoimmune Diseases Research

Background:

  • B-lymphoid tyrosine kinase (BLK) is implicated in autoimmune disorders.
  • The association between BLK gene polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) remains uninvestigated.
  • Understanding genetic factors in NMOSD is crucial for disease management.

Purpose of the Study:

  • To investigate the correlation between B-lymphoid tyrosine kinase (BLK) gene polymorphism, mRNA expression, and NMOSD in the Chinese Han population.
  • To determine the potential protective role of specific BLK polymorphisms against NMOSD.
  • To analyze the relationship between BLK mRNA levels and NMOSD clinical status.

Main Methods:

  • Genotyping of three single nucleotide polymorphisms (SNPs) in the BLK gene (rs13277113, rs4840568, rs2248932) in 310 subjects.
  • Analysis of allele, genotype, and haplotype frequencies, including stratified analysis by clinical characteristics.
  • Quantification of BLK mRNA expression in peripheral blood mononuclear cells (PBMCs) from 64 subjects using real-time PCR.

Main Results:

  • The minor allele G of rs2248932 in BLK was associated with reduced NMOSD susceptibility (OR=0.57, P=0.003).
  • This protective association was particularly evident in the AQP4-positive subgroup (OR=0.46, P=0.001).
  • BLK mRNA expression was lower in NMOSD patients overall but significantly higher in acute, untreated individuals compared to healthy controls.

Conclusions:

  • The minor allele G of rs2248932 in the BLK gene confers protection against NMOSD, especially in AQP4-positive cases.
  • BLK mRNA levels are generally reduced in NMOSD patients, but show a marked increase during acute, untreated phases.
  • BLK gene variations and expression patterns are relevant to NMOSD pathogenesis and clinical presentation.