Genetic risk factors for gout less important with alcohol exposure

Alcohol exposure suppresses the effect of two genetic variants associated with the risk of gout, according to New Zealand research.

The study found an interaction between alcohol and the variant rs7800094 in the GCKR gene which encodes for glucokinase regulatory protein, as well as the rs10821905 variant of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1, complementation factor (A1CF) gene.

The effect was noted in people of European descent but not in Maori or Pacific Islander people.

Co-author Professor Tony Merriman, from the University of Otago’s School of Biomedical Sciences, told the limbic the findings did not change any management strategies or advice to patients regarding alcohol consumption.

However it did advance understanding of the important relationship between the genetic and environmental components of gout and why alcohol triggers gout in some patients but not others.

He said the findings, from almost 3,000 people, showed that one mechanism for alcohol’s action on gout risk was via metabolic pathways in the liver.

“The GCKR gene acts as a gatekeeper to the production of gout-causing metabolites in people not drinking alcohol. However the gene is overwhelmed in people who are drinking alcohol,” he said.

He said the A1CF gene, through its role in apolipoprotein metabolism, regulated levels of very low-density lipoprotein (VLDL).

“There is genetic and epidemiological evidence to implicate VLDL in gout – potentially as the final trigger for immune recognition of uric acid crystals.”

“Long-term, this might re-emphasise the role of lipid lowering drugs such as fibrates in gout management.”

The study, which looked at 29 urate-associated genetic variants, found no interaction between alcohol and genes such as SLC2A9 or ABCG2, which relate to uric acid excretion.

“Eventually we hope to be able to predict which environmental factors are worse for one patient versus another and open up new intervention pathways.”

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