Single-nucleotide polymorphisms of tight junction component claudin-1 associated with leukoaraiosis

Background The blood-brain barrier (BBB) plays a major role in the development of leukoaraiosis (LA). The junctional complex of BBB consists of tight junction (TJ) and adherens junction (AJ). Claudin-1 is the integral component of TJ. The aim of this study was to evaluate whether genetic variations in claudin-1 gene are associated with the development of LA. Methods LA has to be diagnosed based on images. A total of 228 LA cases and 203 controls were enrolled from the individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of claudin-1 single-nucleotide polymorphisms (SNPs) (rs17501010, rs893051, and rs9290927) was performed by real-time polymerase chain reaction with LightSNiP reagents (coupled primer and probe) and FastStart DNAMaster HybProbe (Roche Diagnostic, GmBH, Mannheim, Germany) in LightCycler 2.0. Results Among the 3 SNPs of claudin-1, a significant genetic difference was found only between control and LA (both LA-periventricular white matter [PVWM] and LA-subcortical deep white matter) with SNP rs9290927. However, their haplotypes G-G-T and G-C-A were significantly different between LA-PVWM and control, which increase the development of LA-PVWM with odds ratios of 1.45 and.57, respectively. Conclusions This study demonstrated first evidence of genetic polymorphism of TJ component claudin-1 and their haplotypes associated with LA.