Common susceptibility variants of KDR and IGF-1R are associated with poststroke depression in the Chinese population

Abstract

Background Depression, one of the most frequent complications after stroke, increases the disease’s burden and physical disability. Poststroke depression (PSD) is a multifactorial disease with genetic, environmental and biological factors involved in its occurrence. Genetic studies on PSD to date have mainly focused on the monoamine system and brain-derived neurotrophic factors. However, understanding is still limited about the influence of the single nucleotide polymorphism (SNP) of other neurotrophic factors on PSD.Aims The present study aimed to investigate the relationship between seven vascular endothelial growth factor (VEGF) family gene variants that occur with PSD.Methods A multicentre candidate gene study from five hospitals in Jiangsu Province from June 2013 to December 2014 involved 121 patients with PSD and 131 patients with non-PSD. Demographic characteristics and neuropsychological assessments were collected. The χ2 test was used to evaluate categorical variables, while the independent t-test was applied to continuous variables. SNPs in seven genes (VEGFA, VEGFB, KDR, FLT-1, IGF-1, IGF-1R and PlGF) were genotyped. Single-marker association for PSD was analysed by χ2 tests and logistic regression using SPSS and PLINK software.Results Patients with PSD included more women and those with lower education levels, lower body mass indexes, lower Mini-Mental State Examination scores, and higher scores on the 17-item Hamilton Depression Rating Scale than non-PSD patients. Ninety-two SNPs with seven genes were genotyped and passed quality control. The rs7692791 CC genotypes, the C allele of KDR and the rs9282715 T allele of IGF-1R increased the risk for PSD (χ2=7.881, p=0.019; χ2=4.259, p=0.039; χ2=4.222, p=0.040, respectively). In addition, the SNP rs7692791 of KDR was significantly associated with PSD by the logistic regression of an additive model (p=0.015, OR=9.584, 95% CI: 1.549 to 59.31).Conclusions Patients with rs7692791 C allele carriers or the CC genotype of KDR and the rs9282715 T allele of IGF-1R may have PSD susceptibility. Findings such as these may help clinicians to identify the high-risk population for PSD earlier and, thus, enable them to provide more timely interventions.Trial registration number ChiCTR-OCH-13003133.