Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment Among Eastern Indians

AbstractPost-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes,BDNF and (b) dysregulation in expression level ofCLOCK, BMAL1, andBDNF that may be associated with PSCI.BDNF (rs6265G/A, rs56164415C/T),CLOCK (rs1801260T/C, rs4580704G/C), andCRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its ‘C’ allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the ‘CC’ genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression forCLOCK andBDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. U...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research