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

Abstract

To investigate the methylation status in promoter region of estrogen receptor alpha (ERа)-A gene and its relation with plasma homocysteine (Hcy) level and cognitive impairment in white matter hyperintensity (WMH) patients. 210 patients aged 65 and older were selected. The methylation status of CpG islands in ERа-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. We found a significant association between the severity of WMH and CpG island methylation of ERа-A gene (P < 0.05). Multiple regression analysis showed that serum Hcy level, methylation of ERа-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 ERа-A gene with serum Hcy level, WMH severity, cognitive function and IADL status (P < 0.05). Methylation of ERа-A gene promoter has a high frequency in WMH patients with cognitive impairment and is correlated with high plasma Hcy level.