Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Introduction & Aim: The most recent hypothesis that explains the development of small vessel disease vascular dementia (VaD) emphasises the role of blood-brain barrier (BBB) dysfunction. However, while environmental risk factors like hypertension and Type 2 diabetes mellitus are known to contribute to BBB dysfunction, the molecular mechanism of this process is unclear. It is hypothesised that certain genetic polymorphisms of the BBB tight junction claudin-1 protein, in combination with adverse environmental risk factors, increase the risk of BBB dysfunction and small vessel disease. Methods: In this case-control study, 47 control participants, with a Mini Mental State Exam (MMSE) score of above 27, and 36 VaD participants were recruited and completed a questionnaire on their medical history and lifestyle factors. Blood was also collected and three single nucleotide polymorphisms (SNPs), rs17501010, rs9290927 and rs893051 of claudin-1 genotyping were analysed by real-time polymerase chain reaction (PCR) assay. Results: A significant higher prevalence was found in the VaD group compared to controls in the GT genotype of SNP rs17501010 (p=0.011) and the AT genotype of SNP rs9290927 (p=0.012). Stratified analysis also showed that individuals with both the variant genotype of any of the 3 SNPs (rs17501010, rs9290927 and rs893051) of claudin-1 and Type 2 diabetes mellitus, have a significantly higher risk of developing small vessel VaD. Conclusion: The claudin-1 polymorphisms rs17501010 and rs9290927 are significantly associated with VaD. Moreover, gene-environment interaction between claudin-1 polymorphisms and Type 2 diabetes mellitus plays a synergistic role on the development of small vessel VaD.

Biography

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