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Swedish Obese Subjects

Post-surgical uric acid changes driven by weight loss

Study finds little evidence for an interaction between genotype and weight change

The latest paper from the Swedish Obese Subjects study group has reported that fluctuations in uric acid levels following bariatric surgery appear to be driven by the weight losses and gains, independent of the patient’s genetic makeup.

Published in the open access journal, Plos One, the research says that there was little evidence for an interaction between a patient’s genotype and weight change on the response of uric acid to bariatric surgery over ten years.

Elevated uric acid levels are associated with an increased risk of mortality and cardiovascular disease, as well as cardiovascular disease risk factors such as obesity, hypertension, dyslipidemia, diabetes and metabolic syndrome. High concentrations of uric acid can lead to gout.

It has been previously reported that obesity and the SLC2A9 genotype are strong determinants of uric acid levels, but little research has gone into the relationship between on SLC2A9 variants and weight loss-induced changes in uric acid levels.

As a result, the researchers examined whether the changes in uric acid levels two- and ten-years after weight loss induced by bariatric surgery were associated with SLC2A9 single nucleotide polymorphisms in the Swedish Obese Subjects study.

Specifically, the investigators wanted to determine whether the changes in uric acid observed with weight fluctuations are conditioned by DNA sequence differences at the SLC2A9 locus.

The study sample was comprised of 1,806 subjects who had undergone Gastric banding, vertical banded gastroplasty, or gastric bypass, and had valid genotype and uric acid concentration data. Changes in uric acid were compared between baseline and two years, and years two and ten.

Results

Uric acid levels significantly decreased from baseline to year two in all subjects, with the gastric bypass group showing a significantly larger mean decrease than the banding procedures groups, which was explained by the greater weight loss in this group (p=0.12 when adjusting for change in weight).

However, levels increased by 28.7±75.1µmol/L from year two to year ten after surgery in all subjects, with no differences between surgical techniques. There were no sex differences in the changes in uric acid levels from baseline to year two. However, females had a significantly (p=0.0005) larger mean increase (33.9±73.7µmol/L) in uric acid levels from year two to year ten compared to males (16.0±90.5µmol/L).

Change in weight was significantly correlated with change in uric acid levels from baseline to year two (r =0.39, p<0.0001) and from year two to ten (r=0.34, p<0.0001). Of the variables measured, change in weight was the strongest predictor of change in uric acid levels after bariatric surgery.

Weight change from baseline to year two explained 14.6% of the variance (βcoeff = 1.72, p<0.0001) in change in uric acid level during the same time period, while weight change from year two to ten explained 11.9% of the variance (βcoeff = 1.84, p<0.0001) in change in uric acid level during the same time period.

Conclusion

“We found that weight changes were the driver of changes in uric acid levels, explaining less than 15% of the variance in uric acid level changes following bariatric surgery, with SLC2A9 genotype accounting for a negligible proportion (<1%),” the authors write. “Our results indicate that SLC2A9 variants had little effect on the inter-individual variation in the changes of uric acid in response to weight fluctuations induced by bariatric surgery.”

The researchers note that although it appears common SLC2A9 variants do not contribute to uric acid changes in response to weight fluctuation, they cannot exclude other types of gene by weight interaction effects, as only 6% of the variation in serum uric acid can be accounted for by SLC2A9 polymorphisms. They say that further studies are needed to find out if genes aside from SLC2A9 are associated with changes in the level of uric acid in weight loss patients.

“SNPs in the SLC2A9 locus contribute significantly to uric acid levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery,” say the researchers. “However, we found little evidence for an interaction between genotype and weight change on the response of uric acid to bariatric surgery over ten years. Thus, the fluctuations in uric acid levels among the surgery group appear to be driven by the weight losses and gains, independent of SLC2A9 genotypes.”

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