Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents

Abstract

Abstract The glucokinase regulator gene (GCKR) is located on chromosome 2p23. It plays a crucial role in maintaining plasma glucose homeostasis and metabolic traits. Recently, genome-wide association studies have revealed a positive association between hyperuricemia and GCKR variants in adults. This study investigated this genetic association in Taiwanese adolescents. Data were collected from our previous cross-sectional study (Taipei Children Heart Study). The frequencies of various genotypes (CC, CT, and TT) or alleles (C and T) of the GCKR intronic single-nucleotide polymorphism (SNP) rs780094 and the coding SNP rs1260326 (Pro446Leu, a common 1403C-T transition) were compared between a total of 968 Taiwanese adolescents (473 boys, 495 girls) with hyperuricemia or normal uric acid levels on the basis of gender differences. Logistic and linear regression analyses explored the role of GCKR in abnormal uric acid (UA) levels. Boys had higher UA levels than girls (6.68 ± 1.29 and 5.23 ± 0.95 mg/dl, respectively, p < 0.001). The analysis of both SNPs in girls revealed that the T allele was more likely to appear in patients with hyperuricemia than the C allele. After adjusting for confounders, the odds ratio (OR) for hyperuricemia incidence in the TT genotype was 1.75 (95% confidence interval [CI] 1.02–3.00), which was higher than that in the C allele carriers in rs1260326 in the girl population. Similarly, the TT genotypes had a higher risk of hyperuricemia, with an OR of 2.29 (95% CI 1.11–4.73) for rs1260326 and 2.28 (95% CI 1.09–4.75) for rs780094, than the CC genotype in girl adolescents. The T (Leu446) allele of GCKR rs1260326 polymorphism is associated with higher UA levels in Taiwanese adolescent girls.