Genetically High Plasma Vitamin C Not Associated With Risk for Hyperuricemia
The SLC23A1 rs33972313 genetic variant can be used to explore the plasma vitamin C-plasma urate relationship.
High plasma vitamin C is associated with low plasma urate and with a low risk for hyperuricemia, but the SLC23A1 rs33972313 genetic variant that causes lifelong high plasma vitamin C is not associated with plasma urate levels or with risk for hyperuricemia, which suggests that there is no causal relationship between high plasma vitamin C levels and low plasma urate levels, according to the results of an observational analysis and a Mendelian randomization study published in Rheumatology.
The study investigators tested the hypothesis that high plasma vitamin C levels are causally associated with low plasma urate levels and a low risk for hyperuricemia. They measured plasma urate levels and genotyped for the SLC23A1 rs33972313 vitamin C variant in 106,147 individuals from the Copenhagen General Population Study, of whom 24,099 had hyperuricemia. In addition, they measured plasma vitamin C levels in 9234 individuals and genotyped for the SLC2A9 rs7442295 urate variant in 102,335 individuals. Overall, 9111 individuals had both plasma urate and vitamin C measurements performed.
After multivariate adjustments, each 10 μmol/L higher level of plasma vitamin C was associated with a −2.3 μmol/L lower plasma urate level (95% CI, −0.69 to −3.9 μmol/L). The SLC23A1 rs33972313 GG genotype was associated with a 9% higher plasma vitamin C level (95% CI, 5.6%-11.9%) compared with the AA and AG variants combined, but was not associated with plasma urate levels (P =.31).
In a similar fashion, for each 10 μmol/L higher level of plasma vitamin C, the odds ratio (OR) for hyperuricemia was 0.92 (95% CI, 0.86-0.98) observationally after multivariate adjustments, whereas the OR was 1.01 (95% CI, 0.84-1.23) genetically.
The investigators noted that this was the largest study to analyze the observational associations between plasma vitamin C and plasma urate levels, as well as the first study to apply the Mendelian randomization design to determine whether vitamin C exerts an effect on urate levels in the general population. Based on the study results, vitamin C supplementation should possibly not be recommended as a treatment regimen for lowering plasma urate levels.
Kobylecki CJ, Afzal S, Nordestgaard BG. Genetically high plasma vitamin C and urate: a Mendelian randomization study in 106 147 individuals from the general population [published online June 23, 2018]. Rheumatology (Oxford). doi:10.1093/rheumatology/key171