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

P. Xie; K. Kancherla; S. Chandramohan; N. Braidy; Eunice Kar Wing Chan; Y. H. Xu; Daniel K. Y. Chan

doi:10.1002/agm2.12278

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

P. Xie, K. Kancherla, S. Chandramohan, N. Braidy, Eunice Kar Wing Chan, Y. H. Xu, Daniel K. Y. Chan

Western Sydney University

Research output: Contribution to journal › Article › peer-review

Abstract

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, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 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, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 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.

Original language	English
Pages (from-to)	347-352
Number of pages	6
Journal	Aging Medicine
Volume	6
Issue number	4
DOIs	https://doi.org/10.1002/agm2.12278
Publication status	Published - Dec 2023

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© 2023 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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10.1002/agm2.12278

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@article{c5cc161698324ec28ea2dc6a1de36fed,

title = "Involvement of single nucleotide polymorphisms of junction adhesion molecule with small vessel vascular dementia",

abstract = "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, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 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, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 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.",

author = "P. Xie and K. Kancherla and S. Chandramohan and N. Braidy and Chan, {Eunice Kar Wing} and Xu, {Y. H.} and Chan, {Daniel K. Y.}",

year = "2023",

month = dec,

doi = "10.1002/agm2.12278",

language = "English",

volume = "6",

pages = "347--352",

journal = "Aging Medicine",

issn = "2475-0360",

publisher = "Wiley-Blackwell Publishing",

number = "4",

}

TY - JOUR

T1 - Involvement of single nucleotide polymorphisms of junction adhesion molecule with small vessel vascular dementia

AU - Xie, P.

AU - Kancherla, K.

AU - Chandramohan, S.

AU - Braidy, N.

AU - Chan, Eunice Kar Wing

AU - Xu, Y. H.

AU - Chan, Daniel K. Y.

PY - 2023/12

Y1 - 2023/12

N2 - 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, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 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, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 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.

AB - 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, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 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, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 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.

UR - https://hdl.handle.net/1959.7/uws:75828

U2 - 10.1002/agm2.12278

DO - 10.1002/agm2.12278

M3 - Article

SN - 2475-0360

VL - 6

SP - 347

EP - 352

JO - Aging Medicine

JF - Aging Medicine

IS - 4

ER -

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

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