In the Journals

Genetic polymorphisms directly influence gout risk regardless of coffee intake

Although coffee drinking has been previously associated with a decreased risk for gout, researchers found that genetic polymorphisms linked to higher risk of gout and lower coffee consumption predominantly influence gout directly rather than the effects mediated by coffee intake.

“Specifically, alleles in several genes associated with hyperuricemia — GCKR, ABCG2, MLXIPL and CYP1A2 — are also associated with decreased habitual coffee intake,” Joseph Hutton, of the University Auckland, New Zealand, and colleagues wrote. “These four alleles are the sole alleles currently known to be associated with both serum urate, gout risk and habitual coffee consumption from existing genome-wide analysis studies. Regional association plots suggest that the signals for both urate and habitual coffee consumption are very similar for the four loci.”

To find whether the single nucleotide polymorphisms GCKR, ABCG2, MLXIPL and CYP1A2 have a direct affect on the risk for gout through their effects on coffee consumption, the researchers studied information on individuals included in the U.K. Biobank Resource, a database of adults aged between 40 and 69 years with European ethnicity. The researchers identified 130,966 participants with available dietary information — including coffee intake — and genome-wide genotypes. Of those participants, 2,135 had gout.

Researchers found that genetic polymorphisms linked to higher risk of gout and lower coffee consumption predominantly influence gout directly rather than the effects mediated by coffee intake.
Source: Shutterstock

Hutton and colleagues tested gout status and coffee intake for associations with the four single nucleotide polymorphisms. They then conducted multiple regression and a path analysis to determine whether drinking coffee lessened the effect of the single nucleotide polymorphisms on the risk for gout.

According to the researchers, consuming any amount of coffee was inversely associated with gout (adjusted OR = 0.75; 95% CI, 0.67-0.84). In addition, the researchers noted evidence of a dose-effect per cup consumed per day (aOR = 0.85; 95% CI, 0.82-0.87).

The four alleles were associated with decreased daily coffee consumption, with the strongest associations corresponding to CYP1A2 (P= 8×1040) and MLXIPL (P= 3×108). The weaker associations were with GCKR (P= 3×1010) and ABCG2 (P= 2×109). However, although GCKR and ABCG2 were associated with gout (P <5×108), MLXIPL and CYP1A2 were not, the researchers wrote. In their mediation analysis, they found that the direct effects of GCKR and ABCG2 represented most of the total effect on the risk for gout. Their indirect effects mediated by coffee consumption were much smaller, they wrote.

“This work further supports the hypothesis that coffee consumption is protective for gout risk,” Hutton and colleagues wrote. “The exact mechanism of this protective effect remains unclear. Although several SNPs associate with both lower total coffee consumption and higher gout risk, mediation analysis indicates that these SNPs have direct effects on gout risk rather than indirect effects mediated by coffee consumption. The coffee- and urate-associated loci could influence coffee consumption and urate levels, respectively, through separate biological mechanisms.” – by Jason Laday

Disclosure: Hutton reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Although coffee drinking has been previously associated with a decreased risk for gout, researchers found that genetic polymorphisms linked to higher risk of gout and lower coffee consumption predominantly influence gout directly rather than the effects mediated by coffee intake.

“Specifically, alleles in several genes associated with hyperuricemia — GCKR, ABCG2, MLXIPL and CYP1A2 — are also associated with decreased habitual coffee intake,” Joseph Hutton, of the University Auckland, New Zealand, and colleagues wrote. “These four alleles are the sole alleles currently known to be associated with both serum urate, gout risk and habitual coffee consumption from existing genome-wide analysis studies. Regional association plots suggest that the signals for both urate and habitual coffee consumption are very similar for the four loci.”

To find whether the single nucleotide polymorphisms GCKR, ABCG2, MLXIPL and CYP1A2 have a direct affect on the risk for gout through their effects on coffee consumption, the researchers studied information on individuals included in the U.K. Biobank Resource, a database of adults aged between 40 and 69 years with European ethnicity. The researchers identified 130,966 participants with available dietary information — including coffee intake — and genome-wide genotypes. Of those participants, 2,135 had gout.

Researchers found that genetic polymorphisms linked to higher risk of gout and lower coffee consumption predominantly influence gout directly rather than the effects mediated by coffee intake.
Source: Shutterstock

Hutton and colleagues tested gout status and coffee intake for associations with the four single nucleotide polymorphisms. They then conducted multiple regression and a path analysis to determine whether drinking coffee lessened the effect of the single nucleotide polymorphisms on the risk for gout.

According to the researchers, consuming any amount of coffee was inversely associated with gout (adjusted OR = 0.75; 95% CI, 0.67-0.84). In addition, the researchers noted evidence of a dose-effect per cup consumed per day (aOR = 0.85; 95% CI, 0.82-0.87).

The four alleles were associated with decreased daily coffee consumption, with the strongest associations corresponding to CYP1A2 (P= 8×1040) and MLXIPL (P= 3×108). The weaker associations were with GCKR (P= 3×1010) and ABCG2 (P= 2×109). However, although GCKR and ABCG2 were associated with gout (P <5×108), MLXIPL and CYP1A2 were not, the researchers wrote. In their mediation analysis, they found that the direct effects of GCKR and ABCG2 represented most of the total effect on the risk for gout. Their indirect effects mediated by coffee consumption were much smaller, they wrote.

“This work further supports the hypothesis that coffee consumption is protective for gout risk,” Hutton and colleagues wrote. “The exact mechanism of this protective effect remains unclear. Although several SNPs associate with both lower total coffee consumption and higher gout risk, mediation analysis indicates that these SNPs have direct effects on gout risk rather than indirect effects mediated by coffee consumption. The coffee- and urate-associated loci could influence coffee consumption and urate levels, respectively, through separate biological mechanisms.” – by Jason Laday

Disclosure: Hutton reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.