title: Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The clinical trial protocol is available at ClinicalTrials.gov ( NCT01316653 ). Registered 3 March 2011.
authors.affiliation: College of Medicine, Medical University of South Carolina, 96 Jonathan Lucas St, Suite 601, MSC 617, Charleston, SC, 29425, USA.
authors.forename: Kathryn Tully
authors.initials: KT
authors.lastname: Oelsner
authors.affiliation: Center for Quantitative Research, School of Medicine, Vanderbilt University, 2220 Pierce Ave, 571 Preston Research Building, Nashville, TN, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biological Sciences, Vanderbilt University, 1210 BSB, 465 21st Ave S, Nashville, TN, USA.
authors.forename: Sophie Bao-Chieu
authors.initials: SB
authors.lastname: To
authors.affiliation: Department of Anthropology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Non
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, 2200 Children's Way, Doctor's Office Tower 8232, Nashville, TN, 37232-9225, USA. shari.barkin@vanderbilt.edu.|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. shari.barkin@vanderbilt.edu.
authors.forename: Shari L
authors.initials: SL
authors.lastname: Barkin
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D009035:Mothers; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D012463:Saliva / Q000378:metabolism*
keywords: Cysteine biosynthesis; Epigenetics; Hispanic children; Homocysteine; Methionine; Methylation; Obesity