title: Association of genetic polymorphisms of claudin-1 with small vessel vascular dementia.
abstract: The most recent hypothesis of the development of small vessel vascular dementia (VaD) emphasises the role of blood-brain barrier (BBB) dysfunction. 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 VaD. In this case-control study, 97 control participants, with a mean Mini Mental State Exam (MMSE) score of 29.1, and 38 VaD participants were recruited and completed a questionnaire on their medical history and lifestyle factors. Blood was also collected and two single nucleotide polymorphisms (SNPs), rs17501010 and rs893051 of claudin-1 genotyping, were analysed by real-time polymerase chain reaction (PCR) assay. A significantly higher frequency of all rs893051 SNP genotypes (GC and CC) was found in the VaD population (OR=4.8, P=0.006 and OR=6, P<0.001 respectively). Patients with TT genotype of rs17501010 were also more likely to have VaD (OR=3.25, P=0.022). Stratification analysis revealed that having combined haplotype GC+CC of rs893051 and lipid disorders was associated with higher risk of VaD (OR=9.9, P<0.001). For patients with type 2 diabetes the odds ratio of VaD increased significantly in GC+CC genotypes of rs893051 (OR=12.57, P<0.0001) and GT+TT of rs17501010 (OR=5.33, P=0.01).
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Vivek
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Ingham Institute, Liverpool, NSW, Australia.|Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Nady
authors.identifier: http://orcid.org/0000-0002-0497-5572
authors.initials: N
authors.lastname: Braidy
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.|Ingham Institute, Liverpool, NSW, Australia.
authors.forename: Ying Hua
authors.initials: YH
authors.lastname: Xu
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Kiran
authors.initials: K
authors.lastname: Kancherla
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Sashiruben
authors.initials: S
authors.lastname: Chandramohan
authors.affiliation: Faculty of Medicine, Western Sydney University, Macarthur, NSW, Australia.
authors.forename: Eunice Kar Wing
authors.initials: EKW
authors.lastname: Chan
authors.affiliation: Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia.|Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.|Ingham Institute, Liverpool, NSW, Australia.
authors.forename: Daniel Ky
authors.initials: DK
authors.lastname: Chan
mesh_terms: D000369:Aged, 80 and over; D016022:Case-Control Studies; D062445:Claudin-1 / Q000235:genetics*; D015140:Dementia, Vascular / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D062445:Claudin-1
keywords: Alzheimer's disease; blood-brain barrier; brain; vasculature