Background: Fatty liver is associated with abdominal adiposity, insulin resistance, and risk for diabetes and liver disease. Asians Indians have a high prevalence of fatty liver and abdominal visceral adiposity compared to other racial groups, and the causes are not well understood. Circulating microRNAs (miRs) identify latent risk factors for diabetes and biologic mechanisms underlying disease. Previous studies identified associations between circulating microRNAs and obesity in Caucasians. No prior studies evaluated association between circulating microRNAs and fatty liver and abdominal adiposity in Asian Indians.
Hypothesis: Circulating microRNAs are associated with the presence of fatty liver and elevated waist circumference in Asian Indians.
Methods: We studied 136 participants (49% women, age 56 ± 8 years) from the Metabolic syndrome and Atherosclerosis in South Asians Living in America (MASALA) pilot study. Elevated waist circumference at baseline was defined as >90cm for men and >80cm for women. Fatty liver was measured using computed tomography images of the liver and spleen (in Hounsfield units) and was defined as liver to spleen ratio <1. Circulating microRNAs (n=30) were measured from plasma collected during the baseline visit using the Firefly Circulating microRNA assay. Unadjusted and multivariate-adjusted logistic regression models were created.
Results: Elevated waist circumference was present in 115 (85%) and fatty liver was present in 24 (18%). In age and sex adjusted models, miR-423 was inversely associated with elevated waist circumference (p<0.05). This miR was also inversely associated with metabolic syndrome (p<0.1) in the subset of individuals not taking hypertension or diabetes medications (n=88). MiR-146a, miR-146b, miR-197, miR-20b, miR-21, miR-222, and miR-24 were inversely associated with fatty liver (p<0.05 for all). These microRNAs show moderate to high inter-correlations (r=0.4-0.9). None of these miRs were significantly associated with metabolic syndrome or diabetes. MiR-486, which is associated with glycemic impairment and progression in Asian Indians and insulin resistance and response to thiazolidenidones, was positively associated with fatty liver (p<0.1).
Conclusions: We found significant relationships between fatty liver and waist circumference and numerous circulating microRNAs. MicroRNAs inversely associated with fatty liver are correlated and may be co-expressed in order to regulate biologic pathways related to fatty liver. There is no overlap between miRs associated with fatty liver and miRs associated with diabetes and metabolic syndrome. Additional studies are needed to determine whether circulating microRNAs might be useful biomarkers for the detection of fatty liver, which biologic pathways are implicated, and whether there are differences between race/ethnic groups.