Association of homocysteine and polymorphism of methylenetetrahydrofolate reductase with early-onset post stroke depression

Abstract

BackgroundHomocysteine (Hcy) has been indicated to be involved in pathophysiology of post stroke depression (PSD). There is a lack of research to study the relationship between Hcy metabolism genes and PSD. Our study aims to investigate the relationship among Hcy metabolism genes, Hcy, and early-onset PSD.Materials and methodsWe recruited 212 patients with stroke and collected their peripheral blood sample, clinical data, and laboratory test on admission. 12 single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) genes were genotyped by high-resolution melt analysis. PSD was diagnosed by DSM-V at 2 weeks after stroke. Binary logistic regression and haplotype analysis were used to examine the association between Hcy metabolism genes and PSD. Mediation analysis was performed to clarify whether the SNPs exerted their effect on PSD by affecting the Hcy level.Results81 patients were diagnosed with PSD, and the incidence rate was 38.2%. Hcy level in PSD group was significantly higher than it in non-PSD group (p = 0.019). MTHFR rs1801133 AA genotype an A allele were associated with an elevated risk of PSD after adjustment for some confounding factors (OR = 4.021, 95% CI: 1.459∼11.080, p = 0.007 for AA genotype; OR = 1.808, 95% CI: 1.172∼2.788, p = 0.007 for A allele). Furthermore, the effect of MTHFR rs1801133 AA genotype on PSD was mediated by Hcy (OR = 1.569, 95% CI: 0.013∼3.350, p < 0.05).ConclusionMTHFR rs1801133 and Hcy were associated with PSD, and MTHFR rs1801133 may exert an effect on PSD via mediating Hcy level. This offers a new perspective for treating PSD and understanding the mechanism of PSD.

Lesion location and serum levels of homocysteine are associated with early‐onset post‐stroke depression in acute ischemic stroke

“…Consistent with our findings, Tang et al (2016) and J. Zhang et al (2022) reported that elevated serum levels of HCY at admission were related to depression 2 weeks and 6 months after the stroke onset. Through meta-analysis, Y. Chen et al ( 2022) also found that serum levels of HCY could be used as a biomarker for the prediction for the risk of early-onset PSD.…”

“…(2016) and J. Zhang et al. (2022) reported that elevated serum levels of HCY at admission were related to depression 2 weeks and 6 months after the stroke onset. Through meta‐analysis, Y. Chen et al.…”

The association between circulating Hcy and Lp-PLA2 levels and poststroke depression: A meta-analysis

“…Twenty papers included a total of 3714 stroke patients, 1560 with PSD and 2245 with non-PSD. [10,11,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Twenty papers had NOS scores of 4-9, 12 papers had ≥7, and the percentage of high-quality literature was 60%. The basic characteristics of the literature are shown in Table 1.…”