Changes in Uric Acid Levels following Bariatric Surgery Are Not Associated with SLC2A9 Variants in the Swedish Obese Subjects Study

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.

Weight Loss, Xanthine Oxidase, and Serum Urate Levels: A Prospective Longitudinal Study of Obese Patients

“…In particular, we did not find any correlation between improved insulin resistance, as assessed by the HOMA-IR, and reduced SUA levels. Contrary to what is generally accepted to be true (16,25), this lack of correlation, also reported in another study (14), suggests that reduced SUA levels after bariatric surgery may not be explicable by increased uric acid renal clearance resulting from the improved insulin resistance in such patients (25).…”

“…The SLC2A9 variants, known to be closely associated with SUA levels (23,24), were recently found to have no role in changed SUA levels in response to weight loss after bariatric surgery (25).…”

Quantile-Dependent Expressivity of Serum Uric Acid Concentrations

“…Our reliance on the simple formula h 2 = 2 β OP /(1 + r spouse ) and h 2 = {(1 + 8 r spouse β FS ) 0.05 − 1}/(2 r spouse ) to estimate heritability [ 32 ] is unlikely to embody the true complexity of uric acid inheritance. Our reinterpretations of the results presented by Das Gupta et al [ 37 ], Yang et al [ 42 , 51 ], Lin et al [ 43 ], Sarzynski et al [ 47 ], Cheng et al [ 48 ], Brandstätter et al [ 49 ], and Hamajima and colleagues [ 52 ] do not disprove their original explanations, rather they suggest an alternative interpretation that warrants consideration.…”

“…Bariatric surgery reduces serum uric acid concentrations. Sarzynski et al [ 47 ] reported that uric acid reductions following bariatric surgery were affected by SLC2A9 rs13113918, a coding SNP that produces a synonymous substitution (Leu79Leu). Specifically, the histogram in Figure 3(e) (estimated from their figure 2 ) shows that the number of rs13113918 minor (A) alleles significantly affected two-year decreases in uric acid concentrations after 29 kg weight loss ( P interaction = 0.04).…”

Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

“…The underlined genetic variants were found in our cohort. References to studies relating to genetic variants in this figure: p. R294H and p.I168I [ 22 ], p.L108L [ 31 ], c.535 + 67A > G [ 23 ], p.N82N [ 18 ], p.H86H [ 19 ], p.C258T and p.C426T [ 32 ], p.L75R [ 33 ], p.T125M [ 34 ], p.R171H [ 35 ], p.T467M and p.L415_G417del [ 29 ], p.R434M [ 36 ]. Foot and kidney images were copied from Servier Medical Art, by Servier ( ; kidney image: ; foot image: ) and adapted for the purposes of this article.…”