Association of Genetic Variation in a Wnt Signaling Pathway Gene (β-Catenin) with Susceptibility to Leukoaraiosis

Aim: Blood-brain barrier (BBB) disruption is the primary initiating cause of cerebral small-vessel diseases including leukoaraiosis (LA). β-Catenin is a key regulator of the BBB and plays an important role in cell-cell adhesion at adherens junctions by interacting with cadherin molecules. Thus, β-Catenin may be a good candidate gene for LA. We performed a genetic analyses to investigate the association between β-catenin alleles and LA. Materials and Methods: A total of 339 LA cases and 203 controls were enrolled from individuals who underwent brain magnetic resonance imaging with obtainable vascular risk factors. Genotyping of β-catenin single nucleotide polymorphisms (SNPs), including rs1880481 C > A, rs13072632 C > T, and rs4135385 A > G, was performed by real-Time polymerase chain reaction using a LightCycler 2.0. Results: Two SNPs, rs1880481 and rs4135385, showed significant differences in their allelic frequencies between the control and LA groups and the combinatorial effects of the risk alleles for these two SNPs also significantly increased the risk of LA. The G-T-A, A-T-A, and A-T-G haplotypes for the three SNPs showed significant differences in both types of LA: LA-periventricular white matter and LA-deep white matter. However, the C-T-G haplotype was only significantly different for LA-PVWM, while the A-C-A was only significantly different for LA-DWM. The combination of diabetes mellitis, hypertension, and these risk alleles increased the likelihood of both types of LA. Conclusion: This study provides evidence that β-catenin polymorphisms and their associated haplotypes are associated with susceptibility to LA.