Serum Urate, PUFAs and Abdominal Obesity in Hispanic Children: The Viva La Familia Study

Abstract Objectives Elevated serum urate is known to increase chronic kidney and cardiovascular disease risk. Studies in adults have shown inverse association between serum urate and n-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA). Here, we aimed to determine the relationship between serum levels of PUFAs and urate in overweight/obese Hispanic children of the Viva La Familia Study (VFS) and then test whether it is mediated by obesity and insulin resistance. Methods VFS was designed to determine the genetic and environmental effects on childhood obesity. n-3 (EPA, alpha-linolenic acid (ALA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) and n-6 (arachidonic acid (AA), linoleic acid (LA), eicosadienoic and docosadienoic acid) PUFAs were measured as part of metabolomic profiling (N = 782). Quantitative genetic and phenotypic analyses were conducted using SOLAR. Mediation analysis was conducted using Baron and Kenny approach with waist circumference (WC), BMIZ and HOMA (measures of obesity and insulin resistance) as mediators. Results Phenotypic correlations showed that serum urate was positively associated with LA (β = 0.08 (0.02), P < 0.0001), ALA (β = 0.03 (0.01), P < 0.05), eicosadienoic (β = 0.09 (0.02), P < 0.0001) and docosadienoic acid (β = 0.04 (0.007), P < 0.0001). Further analysis showed inverse genetic correlations between serum urate and EPA (rhog = −0.30 (0.14), P < 0.05), BMIZ (rhog = 0.45 (0.12), P < 0.005) and waist circumference (rhog = 0.42 (0.11), P < 0.005). The genetic correlation between serum urate and EPA remained significant after adjustment for BMIZ (rhog = −0.27 (0.13), P < 0.05) and HOMA (rhog = −0.23 (0.13), P < 0.05). However, it was no longer significant after adjustment for WC (rhog = −0.21 (0.13), P = 0.10). No statistical significance was observed for other PUFAs. Conclusions Our genetic analysis suggests pleiotropic relationship between EPA and serum urate levels as observed in adults. This relationship seems to be mediated by WC, a surrogate measure for abdominal obesity, but not by BMIZ or HOMA. Further investigations are warranted to determine the role of EPA in reducing serum urate and its implications for associated diseases. Funding Sources NIDDK.