The genetics of
messenger RNA (
mRNA) expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to
microRNA (
miRNA) expression. We examined natural variation of
miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for
metabolic syndrome (MetSyn) phenotypes as part of the
Metabolic Syndrome in Men (METSIM) study. We genotyped the subjects using high-density single-nucleotide polymorphism microarrays and quantified the
mRNA abundance using genome-wide expression arrays and
miRNA abundance using next-generation sequencing. We reliably quantified 356
miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed
miRNAs. We mapped the
miRNA abundance as an expression quantitative trait and determined cis regulation of expression for nine of the
miRNAs and of the processing of one
miRNA (miR-28). The degree of genetic variation of
miRNA expression was substantially less than that of mRNAs. For the majority of the
miRNAs, genetic regulation of expression was independent of the expression of
mRNA from which the
miRNA is transcribed. We also showed that for 108
miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24
miRNAs to be significantly associated with MetSyn traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit
acetyl coenzyme A carboxylase β, a key
fatty acid oxidation
enzyme that has been shown to play a role in regulating body fat and
insulin resistance in adipose tissue.