Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia

Abstract

A case-control study was performed to examine the association between vascular dementia and the polymorphisms of the human gene encoding sterol regulatory element binding protein-2 (SREBF2) that regulates cholesterol metabolism. The 16 genetic variants of SREBF2 were identified in 24 Koreans, and 5 out of 16 variants were genotyped in 207 vascular dementia patients and 207 control subjects. Significant association with vascular dementia was shown in 34995G/T with the GT genotype (odds ratio [OR] = 1.57; 95% CI = 1.04-2.37; P < 0.05) and the GG genotype (OR = 0.65; 95% CI = 0.44-0.96; P < 0.05). The CGC, the most common haplotype combined with three SNPs, 24489C/T, 34995G/T, and 68891C/T, was associated with the disease (OR = 0.72; 95% CI = 0.53-0.97; P < 0.05), and the individuals with the CGC might be less susceptible to vascular dementia than those carrying any haplotype including at least one minor allele. This study implied that the variants of SREBF2 might be genetic factors involved in the pathogenesis of vascular dementia.

The Gene Encoding Transforming Growth Factor β1 Confers Risk of Ischemic Stroke and Vascular Dementia

“…The stoke patients with dementia were excluded based on the criteria described in Kim et al 3 A total of 271 patients with ischemic stroke were further categorized into its subtypes using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. 4 As a result, 95 patients had large artery atherosclerosis, 110 had small vessel occlusion (SVO), and 20 had cardioembolism.…”

“…Forty-six cases were diagnosed as stroke with other determined etiology or stroke of undetermined etiology. For details on the patients with vascular dementia and control subjects, see Kim et al 3 Written informed consent was obtained from all subjects. The study protocol was approved by the ethical committee.…”

Genome-wide association study of CSF biomarkers Aβ 1-42 , t-tau, and p-tau 181p in the ADNI cohort

“…38 Overexpression of SREBF2 in cortical neurons of transgenic mice was associated with mitochondrial cholesterol accumulation, increasing susceptibility to A␤ induced oxidative stress and release of apoptogenic proteins 39 and this gene was previously hypothesized as a genetic factor involved in the pathogenesis of vascular dementia. 40 Although relatively large for a CSF study, a limitation of this report is the modest sample size for a GWAS, which precluded stratified analyses for each diagnostic group or as a function of biomarker results. Hopefully, larger studies in the future will be able to incorporate such analyses.…”

An Interactive Association of Common Sequence Variants in the Neuropeptide Y Gene With Susceptibility to Ischemic Stroke

“…6 -29 In light of previous findings, most selected sequence variants were treated as putative functional variants. The single nucleotide polymorphisms (SNPs) in SREBF2 21 and VEGF 28 genes were also probable variants as identified in previous studies on vascular dementia. The gene encoding leukemia inhibitory factor (LIF) was selected as a good candidate because it could modulate neuronal function during development 30 and promote neuronal survival after a cerebrovascular event.…”