P1.03 Progesterone may be a regulator and B12 could be an indicator of the proximal D4Z4 repeat methylation status on 4q35ter

Abstract

FSHD patients have hypomethylation; different course in males and females was linked to sex hormones. We hypothesized that sex hormones, estradiol, testosterone, progesterone, and prolactin might be associated with methylation status of proximal part of D4Z4. We also investigated fT3, folic acid and vitB12 levels. DNA was extracted from 28 FSHD patients and 28 controls for bisulfite methylation analysis, and serum was separated for biochemical analysis of estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12. Methylation analysis was specified to DR1, 5P regions, and proximal region covering both DR1 and 5P. Methylation was compared between patients and controls. Then correlation of methylation with estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 was investigated. We found that 5P and proximal region, but not DR1, were significantly hypomethylated in patients compared to controls. Male patients had significant hypomethylation compared to male controls. Older FSHD patients exhibited notable decrease in fT3 levels and hypomethylation of 5P region. Analyses of each CpG revealed seven hypomethylated positions significantly different from controls. Two of the positions demonstrated correlation with progesterone in controls. Except for one position, methylation levels were inversely correlated with B12 in patients. The results indicate that methylation of proximal D4Z4 region, particularly specific positions, may be associated with progesterone.