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INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program

TitleINSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program
Publication TypeJournal Article
Year of Publication2018
AuthorsPirini, F, Rodriguez-Torres, S, Ayandibu, BG, Orera-Clemente, M, Gonzalez-de la Vega, A, Lawson, F, Thorpe, R. J., J, Sidransky, D, Guerrero-Preston, R
JournalMol Med Rep
Date PublishedJan
ISBN Number1791-2997
Accession Number29138870
Keywords*DNA Methylation, Adolescent, Adult, Aged, Child, Gene Frequency, Genetic Association Studies, Humans, Intracellular Signaling Peptides and Proteins/*genetics, Membrane Proteins/*genetics, Middle Aged, Obesity/diet therapy/*genetics, Polymorphism, Single Nucleotide, Treatment Outcome, Weight Loss/*genetics, Weight Reduction Programs, Young Adult

Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Dietinduced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a nonsurgical weight loss regimen. The present study included 105 obese participants that were enrolled in a personalized weight loss program based on their allelic composition of the following five energy balance and lipid metabolismassociated loci: Near insulininduced gene 2 (INSIG2); melanocortin 4 receptor; adrenoceptor beta2; apolipoprotein A5; and Gprotein subunit beta3. The present study investigated the association between a global DNA methylation index (GDMI), the allelic composition of the five energy balance and lipid metabolismassociated loci, and weight loss during a 12 month program, after controlling for age, sex and body mass index (BMI). The results demonstrated a significant association between the GDMI and near INSIG2 locus, after adjusting for BMI and weight loss, and significant trends were observed when stratifying by gender. In conclusion, a combination of genetic and epigenetic biomarkers may be used to design personalized weight loss interventions, enabling adherence and ensuring improved outcomes for obesity treatment programs. Precision weight loss programs designed based on molecular information may enable the creation of personalized interventions for patients, that use genomic biomarkers for treatment design and for treatment adherence monitoring, thus improving response to treatment.