Hypermethylation of ERa-A gene and high serum homocysteine level are correlated with cognitive impairment in white matter hyperintensity patients

Abstract

Objective: To investigate the methylation status in promoter region of estrogen receptor alpha (ERa)-A gene and its relation with plasma homocysteine (Hcy) level and cognitive impairment in white matter hyperintensity (WMH) patients. Patients and Methods: 210 patients aged 65 and older were selected. The methylation status of CpG islands in ERa-A gene promoter was analyzed by nested methylation-specific PCR. Serum Hcy and estradiol levels were measured by enzyme-linked immunosorbent assay. Cognitive function were evaluated using minimum mental state examination, the montreal cognitive assessment, Stroop color-word test, symbol digit modalities, trail making test B and instrumental activities of daily living (IADL). The severity of WMH was evaluated with the Fazekas scale by brain magnetic resonance imaging. Results: We found a significant association between the severity of WMH and CpG island methylation of ERa-A gene (P < 0.05). Multiple regression analysis showed that serum Hcy level, methylation of ERa-A gene and WMH severity were significant determining factors for cognitive impairment (P < 0.05). The spearman rank correlation analysis showed a significant correlation of methylation of ERa-A gene with serum Hcy level, WMH severity, cognitive function and IADL status (P < 0.05). Conclusion: Methylation of ERa-A gene promoter has a high frequency in WMH patients with cognitive impairment and is correlated with high plasma Hcy level.