Genetic factors influence gout risk independent of obesity, overweight status
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Among individuals with European ancestry, genetic variants demonstrate a strong impact on gout risk in those with overweight or obese BMI, with a similar effect seen in those with normal or low BMI, according to data published in Arthritis & Rheumatology.
“The importance of genetic factors in the development of hyperuricemia and gout has been uncovered in the past decade,” Vicky Tai, MBChB, of the University of Auckland, in New Zealand, and colleagues wrote. “Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with serum urate levels, some of which are also associated with gout. Many of the identified loci include genes encoding renal and gut urate transporters. Among these, SLC2A9 and ABCG2 have the strongest effect on serum urate and gout risk.”
“Although some studies have investigated interactions between BMI and genetic variants on serum urate concentrations and gout, it is currently unclear whether serum urate-associated genetic variants differentially contribute to gout risk according to BMI,” they added.
To analyze whether genetic variants associated with urate differ in their impact on gout risk based on BMI, Tai and colleagues studied data from the UK Biobank Resource. Specifically, the researchers examined data from 358,728 individuals aged 40 to 69 years with European ancestry and available genome-wide genotypes. Participants were grouped according to BMI, with those demonstrating less than 25 kg/m2 defined as low or normal BMI, those between 25 kg/m2 and 30 kg/m2 characterized as overweight, and those at 30 kg/m2 or more as obese.
In all, 122,493 included participants were in the low or normal group, 153,563 were categorized as overweight and 82,672 were identified as obese. A total of 7,311 participants across all groups had gout, including 0.5% of the normal or low BMI group, 2% of the overweight BMI group and 4.3% of the obese BMI group. The researchers used logistic regression, through urate genetic risk score, to test gene-BMI interactions for gout association.
According to the researchers, in the low or normal BMI group, the prevalence of gout was 0.77% in those with a genetic risk score equal to or greater than the mean, compared with 0.27% among those with a genetic risk score less than the mean. In the overweight BMI group, gout prevalence was 3.02% among those with scores equal to or greater than the mean, and 1.02% in those with scores less than the mean. Lastly, in the obese BMI group, gout prevalence was 6.23% in those equal to or greater than the mean, and 2.49% in those less than the mean.
A genetic risk score that was equal to or greater than the mean was positively associated with gout, compared with a score that was less than the mean, in the low/normal (OR = 2.89; 95% CI, 2.42-3.47), overweight (OR = 3.09; 95% CI, 2.84-3.36) and obese (OR = 2.65; 95% CI, 2.46-2.86) BMI groups. The effect of genetic risk score on gout risk among those in the obese BMI group was slightly reduced, compared with the overweight BMI group. However, there was no difference in impact between the low/normal and overweight BMI groups, nor between the low/normal and obese BMI groups.
“In this large cohort of European ancestry, we have shown that a higher urate genetic risk score is associated with an increased odds of gout in individuals across all BMI groups,” Tai and colleagues wrote. “This effect is slightly attenuated in obese people compared to overweight people. However, genetic variants have a strong effect on gout risk in those with overweight and obese BMI, with a similar effect to that observed with low/normal BMI.” – by Jason Laday
Disclosure: Tai reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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