Date Published: June 1, 2018
Publisher: JKL International LLC
Author(s): Sha Lu, Zheng Niu, Yueming Chen, Qiaofeng Tu, Yue Zhang, Wenli Chen, Wenjuan Tong, Zhifen Zhang.
To investigate associations between the age of menopause and the DNA methylation levels of two repetitive elements, Alu and LINE-1, we performed plasma DNA extraction on 161 subjects and serum cell-free DNA extraction on 120 subjects. We grouped women by menopausal age as follows: ≤ 48 years (earlier menopause), ≥ 52 years (later menopause), and 48-52 years (control). The DNA methylation levels of Alu and LINE-1 were measured by MethyLight PCR. The results showed that the DNA methylation levels of both Alu and LINE-1 were inversely correlated with menopausal age in the plasma DNA cohort (r = 0.079, P < 0.001 for Alu; r = 0.045, P = 0.007 for LINE-1) as well as in the serum DNA cohort (r = 0.087, P = 0.001 for Alu; r = 0.041, P = 0.026 for LINE-1). Alu methylation levels in both the plasma and serum DNA cohorts and LINE-1 methylation levels in the plasma cohort were remarkably higher in the earlier menopause group than in the later menopause and control groups (P < 0.01 and P < 0.05, respectively). In the serum DNA cohort, the LINE-1 methylation levels in the later menopause group were significantly lower than that in the earlier menopause group and control group (P < 0.05). Therefore, methylation levels of Alu and LINE-1 were significantly associated with menopausal age. Women with earlier menopause showed hypermethylation in both repetitive elements, while women with later menopause showed hypomethylation. These findings suggest that altered DNA methylation in leukocytes and serum cell-free DNA may represent a biomarker of menopausal age.
In the present study, we found a significant association between the methylation levels of two repetitive elements, Alu and LINE-1, and menopausal age in both peripheral blood leukocyte DNA and serum cfDNA. Women with earlier menopause showed hypermethylation in both repetitive elements compared to healthy controls, while women with later menopause showed corresponding hypomethylation. This association did not depend on age, BMI, hypertension, diabetes, or education. These findings suggest that women with different menopausal ages have different levels of methylation of repetitive elements in blood leukocytes and serum cfDNA. In addition, our data also suggest that altered DNA methylation in leukocytes and cfDNA may represent a biomarker of different menopausal age. To our knowledge, this is the first study to investigate associations between the methylation of Alu and LINE-1 and menopausal age.