BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder

AIM: This study aimed to determine the correlation between B‐lymphoid tyrosine kinase (BLK) polymorphism, mRNA gene expression of BLK, and NMOSD in a Chinese Han population. BACKGROUND: B‐lymphoid tyrosine kinase gene expressed mainly in B cells plays a key role in various autoimmune disorders. However, no studies have investigated the association of BLK polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Han Chinese population of 310 subjects were recruited to analyze three single nucleotide polymorphisms (rs13277113, rs4840568, and rs2248932) under allele, genotype, and haplotype frequencies, followed by clinical characteristics stratified analysis. Real‐time PCR was used to analyze mRNA expression levels of BLK in the peripheral blood mononuclear cells of 64 subjects. RESULTS: Patients with NMOSD showed lower frequencies of the minor allele G of rs2248932 than healthy controls (odds ratio (OR) =0.57, 95% confidence intervals (CI) 0.39–0.83, p = 0.003). The association between minor allele G of rs2248932 and reduced NMOSD susceptibility was found by applying genetic models of inheritance (codominant, dominant, and recessive) and haplotypes analysis. Subsequently, by stratification analysis for AQP4‐positivity, the minor allele G frequencies of rs2248932 in AQP4‐positive subgroup were significantly lower than in the healthy controls (OR =0.46, 95% CI 0.30–0.72, p = 0.001). Notably, the genotype GG of rs2248932 was more frequent in AQP4‐negative subgroup (n = 14) than in AQP4‐positive subgroup (n = 93) (p = 0.003, OR =0.05, 95% CI =0.01–0.57). BLK mRNA expression levels in the NMOSD patients (n = 36) were lower than in healthy controls (n = 28) (p < 0.05). However, the acute non‐treatment (n = 7), who were untreated patients in the acute phase from the NMOSD group, showed BLK mRNA expression levels 1.8‐fold higher than healthy controls (n = 8) (p < 0.05). CONCLUSION: This study evaluated that the minor allele G of rs2248932 in BLK is associated with reduced susceptibility to NMOSD and protected the risk of AQP4‐positive. BLK mRNA expression in NMOSD was lower as compared to healthy controls while significantly increased in acute‐untreated patients.