Association between TIMP1 polymorphism and female neuromyelitis optica spectrum disorder in Chinese population

Abstract

Aims: Earlier studies have indicated an association between the TIMP1 polymorphism and the risk of certain autoimmune diseases, as well as a link between higher TIMP1 levels and blood-brain barrier (BBB) disruption in neuromyelitis optica spectrum disorders (NMOSD). This study aimed to explore the correlation between TIMP1 polymorphism and NMOSD phenotypes. Methods: Genotyping of three loci (rs4898, rs2070584, rs6609533) in the TIMP1 gene was performed in 126 NMOSD patients and 213 healthy controls (HCs) from North China using the SNaPshot sequencing technique, and a correlation analysis was done between phenotypes and TIMP1 genotype. Results: The frequency of the rs4898-T, rs2070584-T, and rs6609533-G alleles was significantly higher in NMOSD patients than those in HCs (p < 0.05). Accordingly, the rs4898-TT, rs2070584-TT, and rs6609533-GG genotypes were found at a higher frequency in patients than in controls (p < 0.05). Haplotype analysis showed TIMP1 T-T-G (rs4898-rs2070584-rs6609533) frequency was higher in female NMOSD patients (p = 0.019), and the frequency of T-T-G haplotypes in the BBB disrupted group was higher compared with that in the BBB normal group (p = 0.04). Conclusions: TIMP1 rs4898-T, rs2070584-T, and rs6609533 polymorphism may contribute to the susceptibility of Female NMOSD patients in the Chinese Population. TIMP1 T-T-G (rs4898-rs2070584-rs6609533) haplotype is more common among female NMOSD patients and is linked to heightened disruption of the BBB.

Keywords

• TIMP1
• NMOSD
• Polymorphism
• BBB
• MMP9