April 1, 2017 – We once thought of circulating uric acid levels as mainly a biomarker of kidney disease (or a very rich diet), but research over the past decade suggests that higher than normal levels of uric acid can, in fact, be a cause of some cardiovascular or chronic kidney diseases. Uric acid levels are strongly influenced by a person’s genetics and diet, so understanding genetic risk factors will help to identify who needs to be extra careful about what he or she eats. This is the focus of the Voruganti laboratory at the NRI, which applies nutrigenetics research to ask the question of how our genetic differences affect our uric acid metabolism.
What they did: The latest research, reported by Chittoor et al. (2017), looked at how genetic variation in the children of the Viva La Familia study (which looks at genetic and environmental contributions to childhood obesity in a group of more than 1,000 Hispanic children) was associated with urinary clearance of uric acid. Clearance is an important part of how the body maintains appropriate circulating levels of uric acid. They found a series of genetic variations in the ZNF446 gene that were associated with differences in uric acid clearance. Surprisingly, the ZNF446 protein is not itself involved in uric acid handling; rather, ZNF446 falls into a group of proteins known as transcription factors. These proteins regulate the expression of other genes, “and may be involved in transcription of specific uric acid transporters”, Geetha Chittoor added. Currently, we do not know which of the genes regulated by ZNF446 is responsible for the observed difference in uric acid clearance, but this question will be addressed in future research.
Why it matters: The implications of this study extend beyond measurement of uric acid levels. First, the association of ZNF446 with uric acid clearance in this study group (Hispanic children) was not seen in corresponding studies of adults. This suggests that the impact of some genetic factors affecting uric acid levels changes as we age, and that dietary recommendations might also need to change. Second, ZNF446 is a regulatory protein not directly involved in uric acid metabolism – how it functions to alter uric acid metabolism is not known. Also unknown is whether the mutations identified here are associated with other diseases. These findings underscore the importance of a genome-wide approach; we frequently don’t know all of the players linked to a specific disease and, by focusing on only what we know, can miss important discoveries.
Chittoor G, Haack K, Mehta NR, Laston S, Cole SA, Comuzzie AG, Butte NF, Voruganti VS (2017). Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study. BMC Med Genet. 18:6.