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

<div><h3>Context and Objective</h3><p>Obesity and <em>SLC2A9</em> genotype are strong determinants of uric acid levels. However, data on <em>SLC2A9</em> 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 <em>SLC2A9</em> single nucleotide polymorphisms (SNPs) in the Swedish Obese Subjects study.</p> <h3>Methods</h3><p>SNPs (N = 14) identified by genome-wide association studies and exonic SNPs in the <em>SLC2A9</em> 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.</p> <h3>Results</h3><p>Overall, 11 of the 14 tested <em>SLC2A9</em> 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.</p> <h3>Conclusions</h3><p>SNPs in the <em>SLC2A9</em> 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 <em>SLC2A9</em> genotypes.</p> </div

Associations between changes in serum uric acid levels and <i>SLC2A9</i> SNPs in SOS bariatric surgery patients when number of subjects has been maximized locally.

<p>All models are adjusted for age, sex, and percent change in body weight. β values represent change in changes in uric acid level (µmol/L) per copy of minor allele carried. To convert µmol/L to mg/dL divide values by 59.48.</p

Cross-sectional associations between serum uric acid levels and <i>SLC2A9</i> SNPs in SOS bariatric surgery patients when number of subjects has been maximized locally.

<p>All models are adjusted for age, sex, and body weight. β values represent change in cross-sectional uric acid level (µmol/L) per copy of minor allele carried. To convert µmol/L to mg/dL divide values by 59.48.</p

Basic characteristics of SOS subjects with DNA and data for uric acid levels in the total sample and by surgery group.

<p>Main effect P value is for the main effect of surgery technique on variable of interest. For variables showing a significant main effect of surgery technique, post-hoc pair-wise comparisons were run to test the mean difference between the combined banding group (vertical banded gastroplasty and banding) and gastric bypass group. N represents the number of subjects with DNA and data for uric acid level at each time point. To convert µmol/L to mg/dL divide values by 59.48.</p

Adverse and Excellent Responders to Regular Exercise in DREW^*.

*<p>A postmenopausal woman who follows the <i>2008 Physical Activity Guidelines for Americans</i> expends about 8 kcal/kg/week in her exercise program. The 4 kcal/kg/week is about 50% the current recommendation whereas the 12 kcal/kg/week is about 50% above the recommended dose.</p

Prevalence of Adverse Responders to Regular Exercise in Six Studies.

*<p>% represents the proportion of adverse responders in relation to the total number of subjects exercise trained for each of the four traits.</p

Distribution of the response to the HERITAGE exercise program with adverse responders highlighted in red.

<p>To convert pmol/L of insulin to mU/L, divide by 6.945. To convert mmol/L of HDL-C to mg/dL, divide by 0.02586. To convert mmol/L of triglycerides to mg/dl, divide by 0.01129.</p

Descriptive Data, Including Baseline O₂max and its Response to Training, for the Six Cohorts.

<p>Values are given as mean (SD). O₂max response = post-training O₂max minus baseline O₂max (positive value represents improvement in O₂max).</p><p>All gains in VO₂max are significant at p<0.05.</p

Prevalence of Adverse Responders in HERITAGE.

<p>To convert pmol/L of insulin to mU/L, divide by 6.945. To convert mmol/L of HDL-C to mg/dL, divide by 0.02586. To convert mmol/L of triglycerides to mg/dl, divide by 0.01129.</p

Comparison of the VO2max response to regular exercise between adverse responders and non-adverse responders for each response trait in each study.

<p>Data expressed as means and standard deviations.</p><p>Δ VO2max expressed as the change with exercise training in ml O2 per minute, reported as LS means with age, sex, and baseline VO2max as covariates. Δ VO2max % reported as LS means with age and sex as covariates.</p>†<p>p≤0.05 indicates significant difference in VO2max training response between adverse responders and non-adverse responders.</p