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Abstract
Context and ObjectiveObesity and SLC2A9 genotype are strong determinants of uric acid levels. However, data on SLC2A9 variants and weight loss induced changes in uric acid levels are missing. We 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 (SNPs) in the Swedish Obese Subjects study.MethodsSNPs (N = 14) identified by genome-wide association studies and exonic SNPs in the SLC2A9 gene locus were genotyped. Cross-sectional associations were tested before (N = 1806), two (N = 1664) and ten years (N = 1201) after bariatric surgery. Changes in uric acid were compared between baseline and Year 2 (N = 1660) and years 2 and 10 (N = 1172). A multiple testing corrected threshold of P = 0.007 was used for statistical significance.ResultsOverall, 11 of the 14 tested SLC2A9 SNPs were significantly associated with cross-sectional uric acid levels at all three time points, with rs13113918 showing the strongest association at each time point (R2 = 3.7−5.2%, 3.9×10−22≤p≤7.7×10−11). One SNP (rs737267) showed a significant association (R2 = 0.60%, P = 0.002) with change in uric acid levels from baseline to Year 2, as common allele homozygotes (C/C, N = 957) showed a larger decrease in uric acid (−61.4 µmol/L) compared to minor allele carriers (A/X: −51.7 µmol/L, N = 702). No SNPs were associated with changes in uric acid from years 2 to 10.ConclusionsSNPs 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. 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.
Highlights
Chronic hyperuricemia is the underlying cause of gout, the most prevalent inflammatory arthritis in developed countries [1]
Mean weight loss was about 29 kg from baseline to Year 2 after surgery, whereas subjects regained an average of 7.3 kg of weight from Year 2 to Year 10 after surgery
We examined the association of genome-wide association studies (GWASs)-derived and exonic SLC2A9 variants with serum uric acid levels in severely obese subjects, who lost weight, up to ten years after bariatric surgery
Summary
Chronic hyperuricemia is the underlying cause of gout, the most prevalent inflammatory arthritis in developed countries [1]. Elevated serum 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 the metabolic syndrome [2,3]. Elevated serum uric acid levels are associated with obesity, visceral adiposity, via both increased production and decreased renal excretion of urate. In the Swedish Obese Subjects (SOS) study, serum uric acid levels decreased 15% and 6% two and ten years after bariatric surgery, respectively [16]. There was large inter-individual variation in the changes of uric acid levels to weight loss achieved through bariatric surgery in SOS subjects
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