Involvement of single nucleotide polymorphisms of junction adhesion molecule with small vessel vascular dementia.

Objectives: It is now recognized that blood brain barrier (BBB) leakage occurs in cerebral small vascular disease (CSVD) and plays a significant role in the pathophysiology of vascular dementia. We hypothesized that genetic polymorphisms of junctional adhesion molecule-A (JAM-A) (which may result in compromised structure of tight junction proteins that form the BBB) in combination with cerebrovascular risk factors hypertension, lipid disorders, and type 2 diabetes may result in BBB leakage and increase the individual's risk of CSVD-related dementia.

Methods: In this case-control study, 97 controls with a mean Mini-Mental State Exam (MMSE) score of 29 and 38 CSVD-related vascular dementia participants (mean MMSE score of 19) were recruited. Bloods were collected for the analysis of two common single nucleotide polymorphisms (SNPs) of the JAM-A genotypes rs790056 and rs2481084 using real-time polymerase chain reaction (PCR) assay. Medical history of hypertension, hyperlipidemia, and diabetes was collected for all participants.

Results: Polymorphisms of genotype JAM-A SNP rs790056 showed statistically significant result when the subgroup with hyperlipidemia was analyzed (OR = 3.130,  = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670,  = 0.031 for TC + CC genotypes vs controls). No significant result was found with hypertension. Borderline results of statistical significance were found for JAM-A SNP rs2481084 with hyperlipidemia (OR = 3.210,  = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620,  = 0.069 for TC + CC genotypes vs controls) but not for hypertension. The borderline results might have been due to lack of statistical power because of small sample size.

Conclusions: These results lend further support that cerebrovascular risk factors interact with genetic polymorphisms of BBB proteins to increase the risk of vascular dementia.