Childhood adversities are not a predictors of SSTR4met in alcoholics

Abstract

BackgroundGenome methylation may modulate synaptic plasticity, being a potential background for mental disorder. Adverse childhood experiences (ACEs), known to be frequently reported by patients with alcohol dependence (AD), have been proposed as one of environmental inequities influencing DNA methylation. The study is aiming 1.To assess a promoter region methylation in gene for somatostatin receptor subtype-4 (SSTR4), a receptor for somatostatin, a neurotransmitter engaged in neuroplasticity and memory formation, in patients with AD; 2. To verify if SSTR4 promoter methylation is associated with ACEs and other selected environmental factors. Methodology: 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs; a structured self-reported questionnaire - to measure the sociodemographic and clinical characteristics; a module of Catalogue of Healthy Behavior – to assess nutritional health habits; the Alcohol Use Disorders Identification Test – to assess drinking severity. The SSTR4 promoter region methylation status was performed via methylation-specific PCR, and the genotyping for the SSTR4 rs2567608 functional polymorphism - according to the manufacturer’s standard PCR protocol.ResultsSSTR4 promoter region was found methylated in 21.6% patients with AD and 2.3% controls. None of following characteristics: current age, gender, term and kind of labor, 13 categories of childhood trauma, diet, alcohol drinking severity, age at alcohol drinking initiation, age at onset of problem drinking, cigarette smoking, and SSTR4 rs2567608 was a significant predictor for SSTR4 promoter region methylation.ConclusionsSSTR4 promoter region methylation in here studied participants may be either inherited epigenetic modification or secondary, but not to here assessed variables.

Epigenomic mediation after adverse childhood experiences: a systematic review and meta-analysis

“…Moreover, a case–control study on 176 Polish individuals with ethanol dependence and 127 healthy volunteers found that the former group reported significantly higher numbers of childhood adversities. However, childhood trauma was not found to be a predictor of SSTR4 methylation, despite 21.6% of this population displaying increased SSTR4 promoter methylation compared with 2.3% of controls [ 60 ].…”

The role of childhood adversities, FKBP5, BDNF, NRN1, and generalized self-efficacy in suicide attempts in alcohol-dependent patients

“…ACEs and homozygosity for the major T allele of SSTR4 rs2567608 significantly raise the risk for lifetime suicide attempts in AD patients (i.e., homozygosity remained a significant predictor only in male AD patients) [ 11 ]. One study reported that the promoter region of SSTR4 , which encodes the somatostatin receptor subtype 4, was more frequently methylated in AD patients than in controls; however, SSTR4 promoter region methylation was not associated with the sum of ACEs categories or with any other factor analyzed in that study (term and course of labor, age and sex, nutritional habits, alcohol drinking severity, cigarette smoking) [ 20 ].…”

“…AD patients were invited to participate in the study at least 1 week from the beginning of hospitalization to exclude patients with acute withdrawal syndrome at the time of the study. Of the 209 patients who gave informed consent to participate in the study, 33 did not undergo further analysis because of the following exclusion criteria (of note, some individuals fit multiple exclusion criteria): (1) co-occurring psychiatric disorder requiring current medication ( n = 6); (2) returning an uncompleted study questionnaire ( n = 30); (3) consent withdrawal, primarily due to finding the questions too intimate or time-consuming ( n = 3); (5) prior receipt of chemotherapy consisting of drugs that influence DNA methylation, i.e., 5-azacytidin and decitabine (criterion implemented for the purpose of the previous study on genome methylation ( n = 1) [ 20 ]; and (6) insufficient quality of DNA available ( n = 18).…”

“…AD patients and the controls were native, unrelated inhabitants of Central Poland, recruited into the study between 2013 and 2015 and included in previous studies [ 11 , 20 ].…”

“…Expected environmental factors that may protect a child from a dysfunctional household include change of place of living, change in family structure, and psychological support. However, gene × environment (G × E) studies have provided data that support the hypothesis that susceptibility to the devastating health effects of ACEs throughout the lifespan may be determined by genes encoding proteins that are engaged in memory formation, neuroplasticity, and response to stress, thereby creating an endogenous source of coping skills with life dimensions [ 11 , 17 – 20 ]. For the purpose of the present study, we chose to analyze three functional single nucleotide polymorphisms (SNPs): FKBP5 , BDNF , and NRN1.…”