Age, folate deficiency tied to higher risk of hyperhomocysteinemia

Age and folate deficiency are associated with an increased risk of hyperhomocysteinemia (HHcy), according to a study. This relationship is driven by mediating methylation of the promoter regions of key enzyme genes in the one-carbon metabolism pathway.

“Age and lower folate concentrations are well-known risk factors for cardiovascular disease, but the potential roles of age and folate deficiency in HHcy, especially in HHcy patients with abnormal methylation levels of key enzyme genes promoter in homocysteinemia pathway, have not been thoroughly evaluated,” the investigators said.

To assess the relationship between the promoter methylation levels of six key enzyme genes and age and serum folate level, the investigators analysed these key enzyme genes promoter methylation in 299 HHcy patients through PCR amplification and MethylTarget methods.

The betaine homocysteine methyltransferase (BHMT), Cystathionine β-synthase (CBS), and Methionine synthase gene (MTR) promoter methylation levels showed a positive correlation with age, while CBS promoter methylation level was negatively associated with folate levels. These associations, however, did not reach statistical significance after Bonferroni correction.

In stratified analysis, the methylation level of CBS gene promoter was positively associated with age in males; BHMT gene promoter methylation level also positively correlated with age in HHcy patients with a history of diabetes or hypertension. In addition, stratified analysis according to sex showed that the methylation levels of three CpG regions of BHMT_2, CBS_2, and CBS_3 were positively associated with age in males after Bonferroni correction.