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. 2018 Jan;17(1):1699-1709.
doi: 10.3892/mmr.2017.8039. Epub 2017 Nov 14.

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

Francesca Pirini  1 , Sebastian Rodriguez-Torres  2 , Bola Grace Ayandibu  2 , María Orera-Clemente  3 , Alberto Gonzalez-de la Vega  4 , Fahcina Lawson  2 , Roland J Thorpe Jr  5 , David Sidransky  2 , Rafael Guerrero-Preston  2
Affiliations

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

Francesca Pirini et al. Mol Med Rep. 2018 Jan.

Abstract

Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet‑induced 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 non‑surgical 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 metabolism‑associated loci: Near insulin‑induced gene 2 (INSIG2); melanocortin 4 receptor; adrenoceptor β2; apolipoprotein A5; and G‑protein subunit β3. The present study investigated the association between a global DNA methylation index (GDMI), the allelic composition of the five energy balance and lipid metabolism‑associated 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.

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Figures

Figure 1.
Figure 1.
Inverse association between global DNA methylation and weight loss (P<0.05).
Figure 2.
Figure 2.
(A) The allelic frequency of near INSIG2 (rs7566605) was 50.53, 41.05 and 8.42% for G/G, G/C and C/C, respectively. (B) Boxplots for each near INSIG2 (rs7566605) genotype and their corresponding global DNA methylation index values. INSIG2, insulin-induced gene 2.
Figure 3.
Figure 3.
Boxplots of global DNA methylation index values stratified by genotype for (A) ADRB2, (B) GNB3, (C) APOA5 and (D) MC4R. ADRB2, adrenoceptor β2; GNB3, G-protein subunit β3; APOA5, apolipoprotein A5; MC4R, melanocortin 4 receptor.
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