Abstract:

Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region， thereby providing a scientific basis for stratified clinical management. Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study. The collected data included demographic characteristics， frequency of gout attacks， presence of tophi， levels of uric acid， creatinine， C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， gout-related genes （ABCG2， SLC2A9， SLC22A12， MTHFR）， and joint ultrasound findings. Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity. Results The male-to-female ratio was 11∶1； the mean age was （35.28 ± 2.67） years； the mean disease duration was （6.03 ± 0.68） years； and the mean frequency of acute attacks in the past 12 months was 4 （2.0， 7.25）. Genotype distributions were as follows： ABCG2： wild-type （C/C）， 23.8%； heterozygous （C/A）， 53.2%； homozygous （A/A）， 23%. SLC2A9： wild-type （A/A）， 24.6%； heterozygous （A/G）， 50%； homozygous （G/G）， 25.4%. SLC22A12： wild-type （A/A）， 4.8%； heterozygous （A/C）， 31.7%； homozygous （C/C）， 63.5%. MTHFR： wild-type （C/C）， 68.3%； heterozygous （C/T）， 28.6%； homozygous （T/T）， 3.2%. Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation （ρ = 0.193， P = 0.031） and crystal deposition on ultrasound （ρ = 0.202， P = 0.025）. SLC22A12 polymorphisms were associated with hypertension （ρ = 0.269， P = 0.003） and diabetes （ρ = 0.200， P = 0.026）. MTHFR polymorphisms showed a correlation with diabetes （ρ = 0.224， P = 0.012）. Conclusions Polymorphisms in SLC2A9， SLC22A12， and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients. Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.

Key words: gout, gene polymorphism, stratified clinical management, complication alerts