Genetically high plasma vitamin C and urate: a Mendelian randomization study in 106 147 individuals from the general population

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 - 2018/10/1

Y1 - 2018/10/1

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

SN - 1462-0324

VL - 57

SP - 1769

EP - 1776

JO - Rheumatology

JF - Rheumatology

IS - 10

ER -