Abstract 537: Higher Prevalence of Risk Alleles for Hyperuricemia Parallels Elevated Incidence of Gout and Growing Risk for Cardiovascular Diseases in a Hmong Population

Abstract

Introduction: Hyperuricemia (HU) is the strongest predictor of gout and highly associated with major CVD including hypertension, HF, and CKD. The Hmong, a unique Asian population numbering > 60,000 in Minnesota, have a two-fold increased risk of gout compared to non-Hmong, rising prevalence of CVD, and may differ from other Asian populations in these regards. A genetic predisposition to elevated Serum Uric Acid (SUA) may help identify individuals at risk for gout and CVD. We quantified the Minor Allele Frequencies (MAFs) of known genetic variants (SNPs) associated with HU and compared the MAFs between our Hmong sample and both a reference (HapMap) population of Caucasian (CEU) as well as Han-Chinese (CHB). Methods: Salivary DNA from 235 self-identified Hmong was genotyped using either a Sequenom (iPLEX Gold) or TaqMan approach. MAFs for seven SNPs within candidate genes ( SLC2A9, SLC22A12, PDZK1, and ABCG2 ) identified by GWAS, were determined in our Hmong sample. Associations between HU and genotype were examined for 57/235 Hmong with known SUA levels. A Chi-Square or Fisher exact test with a Bonferroni corrected significance level (<0.007) was used to evaluate MAF differences. Mean SUA concentrations were compared by genotype using one-way ANOVA. Results: Our Hmong participant's age [mean (±SD)] was 30.2 (15.4) years, with >61% overweight or obese and a mean (±SD) SUA of 6.3 (1.7) mg/dL. Although the frequency of risk alleles in the Hmong were significantly higher compared to CEU (6/7) and CHB (3/7) populations, independent SNP by SNP analysis did not show a clear association with SUA. Risk allele frequencies were always more frequent in the Hmong versus comparator groups. Conclusion: MAFs of selected SNPs for HU are not independent of race. The higher prevalence of risk alleles for HU in the Hmong versus CEU and CHB populations may partly explain the clinically observed higher prevalence of gout and CVD risk in the Hmong. Although sample size precludes a robust assessment of an association between genotype and SUA, to our knowledge this is the first study to examine the genetic basis of HU in the Hmong.