Background: The blood–brain barrier disruption plays a major role in the development of leukoaraiosis (LA). Claudins are the integral component of tight junction (TJ). Previous study showed that clauidn-3 and claudin-5 play a significant role in TJ formation and integrity of the BBB. The aim of this study was to evaluate whether genetic variations in claudin-5 gene are associated with the development of LA. Methods: LA has to be diagnosed based on Fazekas Scale and grouped into two classes: periventricular white matter (PVWM) and deep white matter (DWM) . A total of 183 LA-PVWM and 156 LA-DWM cases were enrolled from the individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of claudin-5 single nucleotide polymorphisms (rs1548359, rs10314 and rs739371) was performed by real-time polymerase chain reaction with LightCycler 2.0. Results: The genotypic frequency of claudin-5 and combination effects of 3 SNPs showed no significant different between controls and both type of LA. However, to simplify synergistic allele combinations, the individuals carrying haplotypes C-G-C (rs1548359/rs10314/rs739371) increased development of LA-DWM by 1.44 times of control. Conclusions: This study provides weak evidence of genetic polymorphisms of claudin-5 associated with susceptibility of LA.

SINGLE-NUCLEOTIDE POLYMORPHISMS OF TIGHT JUNCTION COMPONENT CLAUDIN-5 AND LEUKOARAIOSIS