Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

摘要: DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments methyl groups along that are capable modifying gene expression without altering sequencing. The degree to which these patterns heritable, expected range normality across populations, and phenotypic relevance pattern variation remain unclear. Genes regulating metabolic pathways appear be vulnerable ongoing nutritional programming over life course, as dietary nutrients significant determinants methylation, supplying both energy generate process. Here we examine a region leptin (LEP). LEP's putative functions include regulation homeostasis, its signals affecting intake expenditure, adipogenesis storage, lipid glucose metabolism, bone reproductive endocrine function. A differential CpG sites LEP core promoter has been previously identified; however, any consistency or significance not fully elucidated among populations. Using extracted from unfractionated white blood cells peripheral samples, our pilot study, divided into two parts, examined in four populations (phase 1) used biomarkers reflecting leptin's functional process those western Buryat Siberia Mennonite central Kansas, investigate ethnic identified 2). contains binding site for C/EBPα (CCAAT/enhancer protein alpha), tempers final step adipocyte maturity capacity synthesize leptin, TATA motif controlling synthesis. Previous studies report increased this correlated decreased expression, suggesting tissue-specific at ( Melzner et al. 2002 ). We hypothesized evidence would reflect signals: serum levels, lipoproteins transport system, anthropometric measures. In phase 1, combined analyses 313 individuals documented distinct consistent overall seven all ethnicities sexes. This replicates previous studies, conserved Phase 2 (n = 239), correlating transcription (TBS) roles, showed stature, reflects growth remodeling, was significantly inversely percentage suggest plays substantial role metabolism.