Expression Levels of Obesity-Related Genes Are Associated with Weight Change in Kidney Transplant Recipients

BACKGROUND: The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain. METHODOLOGY/PRINCIPAL FINDINGS: A secondary data analysis was done on a subgroup (n = 26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes classifications identified metabolic pathways that were enriched in this dataset. Furthermore, GeneIndexer literature mining analysis identified a subset of genes that are highly associated with obesity in the literature and Ingenuity pathway analysis revealed several significant gene networks associated with metabolism and endocrine function. Polymorphisms in several of these genes have previously been linked to obesity. CONCLUSIONS/SIGNIFICANCE: We have successfully identified a set of molecular pathways that taken together may provide insights into the mechanisms of weight gain in kidney transplant recipients. Future work will be done to determine how these pathways may contribute to weight gain.