Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity

BMC Genomics, Jan 2017

Background The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity. Results Genome-wide DNA methylation was conducted on 92 saliva samples collected from Hispanic preschool children using the Infinium Illumina HumanMethylation 450 K BeadChip (Illumina, San Diego, CA, USA), which interrogates >484,000 CpG sites associated with ~24,000 genes. The analysis was limited to 936 genes that have been associated with obesity in a prior GWAS Study. Child DNA methylation at 17 CpG sites was found to be significantly associated with maternal BMI, with increased methylation at 12 CpG sites and decreased methylation at 5 CpG sites. Pathway analysis revealed methylation at these sites related to homocysteine and methionine degradation as well as cysteine biosynthesis and circadian rhythm. Furthermore, eight of the 17 CpG sites reside in genes (FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1) that have prior known associations with obesity, diabetes, and the insulin pathway. Conclusions Our study confirms that saliva is a practical human tissue to obtain in community settings and in pediatric populations. These salivary findings indicate potential epigenetic differences in Hispanic preschool children at risk for pediatric obesity. Identifying early biomarkers and understanding pathways that are epigenetically regulated during this critical stage of child development may present an opportunity for prevention or early intervention for addressing childhood obesity. Trial registration The clinical trial protocol is available at ClinicalTrials.gov (NCT01316653). Registered 3 March 2011

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Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity

Oelsner et al. BMC Genomics Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at- risk for obesity Kathryn Tully Oelsner Yan Guo Sophie Bao-Chieu To Amy L. Non Shari L. Barkin 0 1 0 Pediatric Obesity Research, Diabetes Research and Training Center, Vanderbilt University School of Medicine , 2200 Children's Way, Doctor's Office Tower 8232, Nashville, TN 37232-9225 , USA 1 Department of Pediatrics, Vanderbilt University School of Medicine , 2200 Children's Way, Doctor's Office Tower 8232, Nashville, TN 37232-9225 , USA Background: The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschoolage children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity. Results: Genome-wide DNA methylation was conducted on 92 saliva samples collected from Hispanic preschool children using the Infinium Illumina HumanMethylation 450 K BeadChip (Illumina, San Diego, CA, USA), which interrogates >484,000 CpG sites associated with ~24,000 genes. The analysis was limited to 936 genes that have been associated with obesity in a prior GWAS Study. Child DNA methylation at 17 CpG sites was found to be significantly associated with maternal BMI, with increased methylation at 12 CpG sites and decreased methylation at 5 CpG sites. Pathway analysis revealed methylation at these sites related to homocysteine and methionine degradation as well as cysteine biosynthesis and circadian rhythm. Furthermore, eight of the 17 CpG sites reside in genes (FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1) that have prior known associations with obesity, diabetes, and the insulin pathway. Conclusions: Our study confirms that saliva is a practical human tissue to obtain in community settings and in pediatric populations. These salivary findings indicate potential epigenetic differences in Hispanic preschool children at risk for pediatric obesity. Identifying early biomarkers and understanding pathways that are epigenetically regulated during this critical stage of child development may present an opportunity for prevention or early intervention for addressing childhood obesity. Trial registration: The clinical trial protocol is available at ClinicalTrials.gov (NCT01316653). Registered 3 March 2011 Obesity; Hispanic children; Epigenetics; Methylation; Methionine; Cysteine biosynthesis; Homocysteine - Background Prevalence of childhood obesity remains a significant public health concern, especially in Hispanic populations who have the higher pediatric obesity rates [1]. Despite having increased risk of developing pediatric and adult obesity compared to other ethnic groups [2], Hispanic children are currently underrepresented in public health research. This is particularly significant as Hispanics are the most populous and rapidly growing ethnic minority in the United States, meaning this population’s health comorbidities secondary to obesity will increase healthcare costs and rates of morbidity [3, 4]. Genetic predisposition, exposure to unhealthy dietary options, and lack of adequate physical activity have all been identified as contributors to pediatric obesity [5]. However, recent literature indicates a more nuanced dynamic mechanism associated with later childhood and adult obesity that reflects the interaction between genetics, environment, and developmental stage via epigenetic modifications [6–8]. While the study of the epigenome is complex, it has the potential to inform the prevention and treatment of pediatric obesity by enhancing our understanding of timing and the mechanisms by which the genetic code could be susceptible to environmental influences [9, 10]. Genetic factors are known to affect multiple cellular and metabolic pathways underlying the development of obesity such as: adipogenesis and fat storage, adipocyte accumulation, the hypothalamic-pituitary adrenal (HPA) system stress response affecting cardiovascular and metabolic health, gastrointestinal tract regulatory signals, orexigenic and anorexigenic and satiety mechanisms, and insulin regulation [11, 12]. For example, there is evidence that adipocyte growth in number and size is established early, by the age of 2, and is indicative of future weight trajectory [13]. Additionally, maternal Body Mass Index (BMI) is correlated with child’s BMI status at age 6 [14] and is a better indicator of child’s BMI trajectory than child birth weight alone [6]. Current maternal BMI has been shown to be significantly associated with current child’s BMI more than other maternal socioeconomic factors (inclu (...truncated)


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Kathryn Oelsner, Yan Guo, Sophie To, Amy Non, Shari Barkin. Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity, BMC Genomics, 2017, pp. 57, 18, DOI: 10.1186/s12864-016-3473-9