RESUMEN
BACKGROUND: The MC3R haplotype C17A + G241A, which encodes a partially inactivated receptor, has high prevalence in individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype. METHODS: A convenience sample of 237 healthy African-American adult volunteers was studied. TaqMan assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex. RESULTS: Individuals homozygous for the MC3R C17A + G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-reactive protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all ps < 0.05); fasting insulin was marginally nonsignificant between groups (p = 0.053). After adjusting for fat mass, laboratory differences no longer remained significant. CONCLUSIONS: Homozygosity for MC3R C17A + G241A is associated with increased adiposity in African-American adults. Further studies are needed to elucidate the mechanisms behind these associations.
Asunto(s)
Adiposidad/genética , Negro o Afroamericano/genética , Inflamación/genética , Receptor de Melanocortina Tipo 3/genética , Adulto , Índice de Masa Corporal , Femenino , Haplotipos , Humanos , Masculino , Adulto JovenRESUMEN
Gene set enrichment analysis (GSEA) is an important step for disease and drug discovery. Genomic, transcriptomics, proteomics and epigenetic analysis of tissue or cells generates gene lists that need to be further investigated in the known biological context. The advent of high-throughput technologies generates the vast number of gene lists that are up or down regulated together. One way of getting meaningful insights of the relationship of these genes is utilizing existing knowledge bases linking them with biological functions or phenotypes. Multiple public databases with annotated gene sets are available for GSEA, and enrichR is the most popular web application still requiring custom tools for large-scale mining. richPathR package is a collection of R functions that helps researchers carry out exploratory analysis and visualization of gene set enrichment using EnrichR.