Hypermethylation of the serotonin transporter gene and paternal parenting styles in untreated anorexia nervosa patients: A pilot study

PURPOSE: It has been reported that serotonergic systems and parenting styles are involved in the pathogenesis of anorexia nervosa (AN). The present study made attempts to examine the DNA methylation profiles in the promoter region of serotonin transporter (5-HTT) encoding gene SLC6A4, and explore the association between the methylation level and severity of symptoms, 5-HTT linked polymorphic region (5-HTTLPR) genotypes and parenting styles in untreated Chinese Han AN patients. METHODS: Ninety-one untreated female AN patients (ANs) and eighty-seven matched healthy controls (HCs) were analyzed for DNA methylation status at CpG islands in the promoter region of SLC6A4 using MassARRY EpiTYPER, and genotypes of 5-HTTLPR using PCR-RFLP. The severity of eating disorder (ED) symptoms was evaluated by body mass index (BMI) and Questionnaire Version of the Eating Disorders Examination (EDE-Q 6.0), and part of participants were assessed parenting styles using the short Chinese Egna Minnen av Barndoms Uppfostra (s-EMBU-C). RESULTS: ANs had greater methylation levels at CpG26.27.28, CpG 31.32, and CpG 37 than HCs (P = 0.039, 0.042, 0.018 respectively). A positive association of methylation level at CpG26.27.28 with ED symptoms detected by EDEQ-6.0 was discovered in AN group (r = 0.216, P = 0.047). Methylation level at CpG26.27.28 was showed to be or tend to be positively correlated with the parenting styles of paternal rejection (r = 0.425, P = 0.038) and paternal overprotection (r = 0.362, P = 0.062) in ANs. No significant differences were found in SLC6A4 promoter region methylation levels among 5-HTTLPR genotypes in our samples (P > 0.05) and no interaction effect between 5-HTTLPR genotypes and parenting styles on SLC6A4 promoter region methylation was observed (P > 0.05). CONCLUSIONS: This study suggested that hypermethylation of SLC6A4 promoter region may be implicated in the pathological mechanisms of untreated Chinese Han female ANs, which is possibly associated with poor parenting styles. This finding may provide a direction for the epigenetic and family treatments for ANs and further investigation with larger samples is warranted.