蒙古族人群ABCG2、GCKR、PRKG2基因多态性及基因-环境交互作用与高尿酸血症的关系OA

Objective To investigate the associations of single nucleotide polymorphisms in the ATP-binding cassette subfamily G member 2(ABCG2)gene rs3114018,glucokinase regulatory protein(GCKR)gene rs780093 and rs780094,and cGMP-dependent protein kinase 2(PRKG2)gene rs7688672 with hyperuricemia(HUA)in the Mongolian population,as well as the impact of gene-gene and gene-environment interactions on the development of HUA.Methods A total of 205 Mongolian patients with HUA were enrolled as the HUA group,and 205 healthy Mongolian volunteers undergoing physical examinations during the same period were matched at a 1:1 ratio as the control group.Clinical data were collected from both groups.Genotypes of ABCG2(rs3114018),GCKR(rs780093,rs780094),and PRKG2(rs7688672)were de-termined using real-time fluorescence quantitative PCR.A Logistic regression analysis was performed to identify factors in-fluencing the occurrence of HUA,and generalized multifactor dimensionality reduction(GMDR)was employed to analyze gene-gene and gene-environment interactions.Results The HUA group exhibited significantly higher body mass index(BMI),serum uric acid,total cholesterol,triglycerides,apolipoprotein A1,apolipoprotein B,homocysteine,and C-reac-tive protein levels,as well as higher rates of smoking,alcohol consumption,and meat-heavy diet than the control group(all P<0.05).Significant differences in the genotype distributions of rs3114018,rs780094,and rs7688672 were ob-served between the two groups(all P<0.05).Multivariate Logistic regression analysis revealed that elevated BMI(OR=1.174,95%CI:1.094-1.261),high triglycerides(OR=1.409,95%CI:1.116-1.779),high homocysteine(OR=1.039,95%CI:1.013-1.066),a history of alcohol consumption(OR=1.929,95%CI:1.040-3.578),and a meat-heavy diet(OR=1.894,95%CI:1.108-3.238)were independent risk factors for HUA(all P<0.05).Conversely,the AC genotype(OR=0.526,95%CI:0.322-0.859)and AA genotype(OR=0.426,95%CI:0.219-0.827)of ABCG2 rs3114018,the TC genotype(OR=0.415,95%CI:0.248-0.693)and CC genotype(OR=0.450,95%CI:0.239-0.847)of GCKR rs780094,and the AG genotype(OR=0.493,95%CI:0.285-0.851)of PRKG2 rs7688672 were inde-pendent protective factors against HUA(all P<0.05).GMDR analysis indicated that the interaction between GCKR rs780094 and rs780093 constituted the optimal gene-gene interaction model(test set accuracy=0.7006,P<0.05).Signifi-cant interactive effects were also identified between environmental factors(e.g.,BMI≥24 kg/m2,smoking history,alco-hol consumption history,and meat-heavy diet)and each gene locus(all P<0.05),with these interactions exerting a great-er effect than the individual gene effects alone.Conclusions The single nucleotide polymorphisms of ABCG2 rs3114018,GCKR rs780094,and PRKG2 rs7688672 are associated with genetic susceptibility to HUA in the Mongolian population,with their mutant alleles acting as protective factors.An interaction exists between the two GCKR loci,and the interactions between genetic and environmental factors jointly influence the occurrence of HUA.