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

Objective: To investigate the methylation status in promoter region of ERа-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 ERа-A gene promoter was analyzed by nested methylation-specific PCR. Serum Hcy and estradiol levels were measured by ELISA. Cognitive function were evaluated using Minimum Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), Stroop color-word test (CWT), symbol digit modalities (SDMT), Trail Making Test (TMT) B and Instrumental Activities of Daily Living (IADL). The severity of WMH was evaluated with the Fazekas scale by brain magnetic resonance imaging (MRI).

Results: 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).

Conclusion: Methylation of ERа-A gene promoter has a high frequency in WMH patients with cognitive impairment and is correlated with high plasma Hcy level.