Genetically high plasma vitamin C and urate: a Mendelian randomization study in 106 147 individuals from the general population
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Genetically high plasma vitamin C and urate : a Mendelian randomization study in 106 147 individuals from the general population. / Kobylecki, Camilla J; Afzal, Shoaib; Nordestgaard, Børge G.
In: Rheumatology, Vol. 57, No. 10, 2018, p. 1769-1776.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetically high plasma vitamin C and urate
T2 - a Mendelian randomization study in 106 147 individuals from the general population
AU - Kobylecki, Camilla J
AU - Afzal, Shoaib
AU - Nordestgaard, Børge G
PY - 2018
Y1 - 2018
N2 - Objective: Gout is the most common form of inflammatory arthritis and is caused by hyperuricaemia. Some studies have found a reduction in plasma urate with vitamin C supplementation. We tested the hypothesis that high plasma vitamin C is causally associated with low plasma urate and low risk of hyperuricaemia, using a Mendelian randomization approach.Methods: We measured plasma urate and genotyped for the SLC23A1 rs33972313 vitamin C variant in 106 147 individuals from the Copenhagen General Population Study, of which 24 099 had hyperuricaemia. We measured plasma vitamin C in 9234 individuals and genotyped for the SLC2A9 rs7442295 urate variant in 102 345 individuals.Results: Each 10 µmol/l higher plasma vitamin C was associated with a -2.3(95%CI: -0.69 to -3.9) µmol/l lower plasma urate after multivariable adjustments. The SLC23A1 rs33972313 GG genotype was associated with a 9% (5.6%, 11.9%) higher plasma vitamin C compared with AA and AG combined but was not associated with plasma urate (P = 0.31). Likewise, for each 10 µmol/l higher plasma vitamin C the odds ratios for hyperuricaemia were 0.92 (0.86, 0.98) observationally after multivariable adjustments, but 1.01 (0.84, 1.23) genetically.Conclusion: High plasma vitamin C was associated with low plasma urate and with low risk of hyperuricaemia. However, the SLC23A1 genetic variant causing lifelong high plasma vitamin C was not associated with plasma urate levels or with risk of hyperuricaemia. Thus, our data do not support a causal relationship between high plasma vitamin C and low plasma urate.
AB - Objective: Gout is the most common form of inflammatory arthritis and is caused by hyperuricaemia. Some studies have found a reduction in plasma urate with vitamin C supplementation. We tested the hypothesis that high plasma vitamin C is causally associated with low plasma urate and low risk of hyperuricaemia, using a Mendelian randomization approach.Methods: We measured plasma urate and genotyped for the SLC23A1 rs33972313 vitamin C variant in 106 147 individuals from the Copenhagen General Population Study, of which 24 099 had hyperuricaemia. We measured plasma vitamin C in 9234 individuals and genotyped for the SLC2A9 rs7442295 urate variant in 102 345 individuals.Results: Each 10 µmol/l higher plasma vitamin C was associated with a -2.3(95%CI: -0.69 to -3.9) µmol/l lower plasma urate after multivariable adjustments. The SLC23A1 rs33972313 GG genotype was associated with a 9% (5.6%, 11.9%) higher plasma vitamin C compared with AA and AG combined but was not associated with plasma urate (P = 0.31). Likewise, for each 10 µmol/l higher plasma vitamin C the odds ratios for hyperuricaemia were 0.92 (0.86, 0.98) observationally after multivariable adjustments, but 1.01 (0.84, 1.23) genetically.Conclusion: High plasma vitamin C was associated with low plasma urate and with low risk of hyperuricaemia. However, the SLC23A1 genetic variant causing lifelong high plasma vitamin C was not associated with plasma urate levels or with risk of hyperuricaemia. Thus, our data do not support a causal relationship between high plasma vitamin C and low plasma urate.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Ascorbic Acid/blood
KW - Female
KW - Genetic Variation
KW - Genotype
KW - Humans
KW - Hyperuricemia/blood
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Odds Ratio
KW - Overnutrition/blood
KW - Risk Factors
KW - Uric Acid/blood
KW - Young Adult
U2 - 10.1093/rheumatology/key171
DO - 10.1093/rheumatology/key171
M3 - Journal article
C2 - 29939348
VL - 57
SP - 1769
EP - 1776
JO - Rheumatology
JF - Rheumatology
SN - 1462-0324
IS - 10
ER -
ID: 217396677