Plasma circulating microRNAs associated with obesity, body fat distribution, and fat mass: the Rotterdam Study.

Abstract

MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression post-transcriptionally and are implicated in the pathogenesis of different diseases. Limited studies have investigated the association of circulating miRNAs with obesity and body fat distribution and their link to obesity-related diseases using population-based data. We conducted a genome-wide profile of circulating miRNAs in plasma, collected between 2002 and 2005, in 1208 participants from the population-based Rotterdam Study cohort. Obesity and body fat distribution were measured as body mass index (BMI), waist-to-hip ratio (WHR), android-fat to gynoid-fat ratio (AGR), and fat mass index (FMI) measured by anthropometrics and Dual X-ray Absorptiometry. Multivariable linear regression models were used to assess the association of 591 miRNAs well-expressed in plasma with these traits adjusted for potential covariates. We further sought for the association of identified miRNAs with cardiovascular and metabolic diseases in the Rotterdam study and previous publications. Plasma levels of 65 miRNAs were associated with BMI, 40 miRNAs with WHR, 65 miRNAs with FMI, and 15 miRNAs with AGR surpassing the Bonferroni-corrected P < 8.46 × 10-5. Of these, 12 miRNAs were significantly associated with all traits, while four miRNAs were associated only with WHR, three miRNAs only with FMI, and miR-378i was associated only with AGR. The most significant association among the overlapping miRNAs was with miR-193a-5p, which was shown to be associated with type 2 diabetes and hepatic steatosis in the Rotterdam Study. Moreover, five of the obesity-associated miRNAs and two of the body fat distribution miRNAs have been correlated previously to cardiovascular disease. This study indicates that plasma levels of several miRNAs are associated with obesity and body fat distribution which could help to better understand the underlying mechanisms and may have the biomarker potential for obesity-related diseases.