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Association of MFSD3 promoter methylation level and weight regain after gastric bypass: assessment for three years after surgery

Nicoletti, C.F., Pinhel, M.A.S., Noronha, N.Y., Jácomo, A., Crujeiras, A.B., Nonino, C.B.
Nutrition 2019
DNA, adipose tissue, analysis of variance, bariatric surgery, body mass index, epigenetics, genes, genetic predisposition to disease, homeostasis, leukocytes, longitudinal studies, methylation, nutrient intake, obesity, patients, solutes, t-test, women
Individual's genetic predisposition and epigenetic signature could explain why some individuals regain the weight lost after different obesity treatments. Major facilitator superfamily domain 3 (MFSD3) is a family of membrane-bound solute carriers that its expression has been recently associated with nutrient intake and adipose tissue homeostasis. This study aimed to evaluate a possible association between MFSD3 preoperative methylation pattern and weight regain after bariatric surgery.This is a longitudinal study comprising 24 obese [Body Mass Index (BMI) >35 m/kg2] women submitted to gastric bypass. Anthropometric measurements were evaluated at preoperative time and one, two and three years after surgery, and then weight regain was calculated. Genomic DNA was extracted from leukocytes and was bisulfite-modified by specific kits, according manufacturer's instructions. Methylation analysis was performed with the Infinium Human Methylation 450K bead chip technology and methylation level was expressed as a beta (β) value [that range from 0 (unmethylated) to 1 (fully methylated)]. Shapiro-Wilk, repeat means ANOVA, Spearman correlation, Mann-Whitney and independent t test were used in statistical analysis (p<0.05).25% of patients regained significant weight. Weight regain after bariatric surgery was positively correlated with cg00010266 MFSD3 preoperative methylation levels (r=0.6804, p=0.0126). Moreover, cg00010266 MFSD3 baseline methylation levels were significant higher in regainers patients than non-regainers (6.2±1.5 versus 3.9±1.2%, p=0.026). Patients allocated in the higher cg00010266 MFSD3 preoperative methylation group showed higher weight regain (4.1±1.8 versus 6.7±2.2 kg, p=0.037).Preoperative hypermethylation of MFSD3 gene is significantly associated with weight regain and than a worse response to gastric bypass.