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Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity
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Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity
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Journal Article
Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity
2024
Overview
Background
Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout.
Methods
This research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses.
Results
Alcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the
ADH1B
locus (
P
= 3.0 × 10
−44
) and rs6460047 at the
MLXIPL
locus (
P
= 1.4 × 10
−4
).
ADH1B
also demonstrated interaction with alcohol consumption for hyperuricaemia (
P
= 7.9 × 10
−13
) and gout (
P
= 8.2 × 10
−9
). Beer intake had the most significant interaction with
ADH1B
for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses,
ADH1B
and
MLXIPL
were associated with serum urate level and
ADH1B
was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers.
Conclusions
In this large study of European participants, novel interactions with alcohol consumption were identified at
ADH1B
and
MLXIPL
for association with serum urate level and at
ADH1B
for association with hyperuricaemia and gout. The association of
ADH1B
with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
