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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.

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 ?2; apolipoprotein A5; and G?protein subunit ?3. 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.

SUBMITTER: Pirini F

PROVIDER: S-EPMC5780113 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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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.

Pirini Francesca F Rodriguez-Torres Sebastian S Ayandibu Bola Grace BG Orera-Clemente María M Gonzalez-de la Vega Alberto A Lawson Fahcina F Thorpe Roland J RJ Sidransky David D Guerrero-Preston Rafael R

Molecular medicine reports 20171114 1

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 ...[more]

PMID: 29138870

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Project description:In a genome-wide association study performed in the Framingham Offspring Cohort, individuals homozygous for the rs7566605 C allele located upstream of insulin-induced gene 2 (INSIG2) were reported to incur an increased risk of obesity. This finding was later replicated in four out of five populations examined. The goal of the study reported here was to assess the role of the INSIG2 single nucleotide polymorphism (SNP) in susceptibility to obesity in the prospective longitudinal Atherosclerosis Risk in Communities (ARIC) study (n = 14,566) and in three other cohorts: the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3,888), the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 4,766), and extremely obese and lean individuals ascertained at the University of Ottawa (n = 1,502). The combined study sample is comprised of 24,722 white, African-American, and Mexican-American participants.Differences in mean body mass index (BMI) and other anthropometric measures including weight, waist circumference, and waist-to-hip ratio were assessed by a general linear model in individuals categorized by INSIG2 rs7566605 genotype. Multivariable logistic regression was used to predict the risk of obesity (BMI >or= 30 kg/m2).There was no discernable variation in the frequencies of the three INSIG2 SNP genotypes observed between white, Hispanic, and African-American obese individuals and non-obese study subjects. When the relationship between rs7566605 and BMI considered either as a categorical variable or a continuous variable was examined, no significant association with obesity was found for participants in any of the four study populations or in a combined analysis (p = 0.38) under a recessive genetic model. There was also no association between the INSIG2 polymorphism and the obesity-related quantitative traits except for a reduced waist-to-hip ratio in white ARIC study participants homozygous for the C allele, and an increased waist-to-hip ratio in African-Americans in the ARIC cohort with the same genotype (p = 0.04 and p = 0.01, respectively). An association with waist-to-hip ratio was not seen when the combined study sample was analyzed (p = 0.74).These results suggest that the INSIG2 rs7566605 variant does not play a major role in determining obesity risk in a racially and ethnically diverse sample of 24,722 individuals from four cohorts.

Project description:BackgroundDigital behavioral weight loss programs are scalable and effective, and they provide an opportunity to personalize intervention components. However, more research is needed to test the acceptability and efficacy of personalized digital behavioral weight loss interventions.ObjectiveIn a 6-month single-arm trial, we examined weight loss, acceptability, and secondary outcomes of a digital commercial weight loss program (WeightWatchers). This digital program included a personalized weight loss program based on sex, age, height, weight, and personal food preferences, as well as synchronous (eg, virtual workshops and individual weekly check-ins) and asynchronous (eg, mobile app and virtual group) elements. In addition to a personalized daily and weekly PersonalPoints target, the program provided users with personalized lists of ≥300 ZeroPoint foods, which are foods that do not need to be weighed, measured, or tracked.MethodsWe conducted a pre-post evaluation of this 6-month, digitally delivered, and personalized WeightWatchers weight management program on weight loss at 3 and 6 months in adults with overweight and obesity. The secondary outcomes included participation, satisfaction, fruit and vegetable intake, physical activity, sleep quality, hunger, food cravings, quality of life, self-compassion, well-being, and behavioral automaticity.ResultsOf the 153 participants, 107 (69.9%) were female, and 65 (42.5%) identified as being from a minoritized racial or ethnic group. Participants' mean age was 41.09 (SD 13.78) years, and their mean BMI was 31.8 (SD 5.0) kg/m2. Participants had an average weight change of -4.25% (SD 3.93%) from baseline to 3 months and -5.05% (SD 5.59%) from baseline to 6 months. At 6 months, the percentages of participants who experienced ≥3%, ≥5%, and ≥10% weight loss were 63.4% (97/153), 51% (78/153), and 14.4% (22/153), respectively. The mean percentage of weeks in which participants engaged in ≥1 aspects of the program was 87.53% (SD 23.40%) at 3 months and 77.67% (SD 28.69%) at 6 months. Retention was high (132/153, 86.3%), and more than two-thirds (94/140, 67.1%) of the participants reported that the program helped them lose weight. Significant improvements were observed in fruit and vegetable intake, physical activity, sleep quality, hunger, food cravings, quality of life, and well-being (all P values <.01).ConclusionsThis personalized, digital, and scalable behavioral weight management program resulted in clinically significant weight loss in half (78/153, 51%) of the participants as well as improvements in behavioral and psychosocial outcomes. Future research should compare personalized digital weight loss programs with generic programs on weight loss, participation, and acceptability.

Project description:BACKGROUND: The Internet is widely available and commonly used for health information; therefore, Web-based weight loss programs could provide support to large parts of the population in self-guided weight loss. Previous studies showed that Web-based weight loss interventions can be effective, depending on the quality of the program. The most effective program tools are visual progress charts or tools for the self-monitoring of weight, diet, and exercises. KiloCoach, a commercial program currently available in German-speaking countries, incorporates these features. A previous investigation showed that the program effectively supports users in losing weight. OBJECTIVE: We investigated weight loss dynamics stratified by weight loss success after 6-month use of KiloCoach. Furthermore, we analyzed possible associations between intensity of program use and weight loss. The results are intended for tailoring user recommendations for weight-loss Internet platforms. METHODS: Datasets of KiloCoach users (January 1, 2008 to December 31, 2011) who actively used the platform for 6 months or more were assigned to this retrospective analysis. Users (N=479) were 42.2% men, mean age of 44.0 years (SD 11.7), with a mean body mass index (BMI) of 31.7 kg/m² (SD 3.2). Based on the weight loss achieved after 6 months, 3 success groups were generated. The unsuccessful group lost <5%, the moderate success group lost 5%-9.9%, and the high success group lost ?10% of their baseline body weight. At baseline, the unsuccessful (n=261, 54.5%), moderate success (n=133, 27.8%), and high success (n=85, 17.8%) groups were similar in age, weight, BMI, and gender distribution. RESULTS: After 6 months, the unsuccessful group lost 1.2% (SD 2.4), the moderate success group lost 7.4% (SD 1.5), and the high success group lost 14.2% (SD 3.8) of their initial weight (P<.001). Multivariate regression showed that early weight loss (weeks 3-4), the total number of dietary protocols, and the total number of weight entries were independent predictors for 6-month weight reduction (all P<.001) explaining 52% of the variance in weight reduction. Sensitivity analysis by baseline carried forward method confirmed all independent predictors of 6-month weight loss and reduced the model fit by only 11%. The high success group lost weight faster and maintained weight loss more efficiently than the other groups (P<.001). Early weight loss was associated with weight maintenance after 1 year and 2 years (both P<.001). Weight dynamics did not differ between men and women over 6 months when adjusted for baseline and usage parameters (P=.91). The percentage of male long-term users was unusually high (42.2%). CONCLUSIONS: Our results suggest that early weight loss and close program adherence (ie, 5 dietary protocols per week and weekly entering of current weight), especially in the early phase of program usage, can improve weight loss outcome.

Dataset Information

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

Publications

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

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