Clinical rheumatology · 2026
Exploring the relationship between XDH gene variants and serum urate and xanthine dehydrogenase levels in gout.
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Román-Olmos Juan Alan, Zamudio-Cuevas Yessica, Martínez-Flores Karina, Espinosa-Morales Rolando, Fernández-Torres Javier
Аннотация
BACKGROUND: Gout is a type of arthritis caused by high levels of urate in the body, leading to inflammation and joint pain. Xanthine dehydrogenase (XDH) is a key enzyme in urate biosynthesis, and genetic variations in its XDH gene can influence the amount or activity of the enzyme, as well as the levels of urate produced.
OBJECTIVES: This study aimed to explore the association of two single nucleotide variants (SNVs) in the XDH gene with gout susceptibility in the Mexican population, as well as their correlation with urate and XDH levels.
METHODS: Genotyping of rs17323225 and rs17011368 XDH SNVs was performed in 41 gout patients and 40 controls using real-time PCR. Urate levels were measured by a colorimetric method, and XDH levels by ELISA. Genotypic distributions were analyzed, and associations were estimated using logistic regression models.
RESULTS: Urate and XDH levels were significantly higher in patients than in controls (p = 0.0004 and p = 0.010, respectively). For the rs17323225 variant, the TT genotype was associated with an increased risk of gout compared to controls (OR = 3.69, 95% CI = 1.06-12.8, p = 0.04). Furthermore, individuals with the TT genotype had higher urate and XDH levels than those with other genotypes (p < 0.001 and p = 0.043, respectively).
CONCLUSION: The rs17323225 variant of the XDH gene may be a genetic risk factor for gout in the Mexican population. These findings suggest that XDH genetic variability contributes to urate metabolism dysregulation and could aid in identifying individuals at higher genetic risk for gout, supporting personalized prevention and treatment approaches. Key Points • Xanthine dehydrogenase (XDH) is an enzyme that catalyzes the sequential conversion of hypoxanthine to xanthine, and of xanthine to urate. • The XDH rs17323225 TT genotype is significantly associated with higher levels of serum urate and XDH, suggesting a functional role in urate biosynthesis. • XDH genotyping may help identify individuals at higher risk of gout and guide tailored urate-lowering or xanthine dehydrogenase-targeted therapies.
OBJECTIVES: This study aimed to explore the association of two single nucleotide variants (SNVs) in the XDH gene with gout susceptibility in the Mexican population, as well as their correlation with urate and XDH levels.
METHODS: Genotyping of rs17323225 and rs17011368 XDH SNVs was performed in 41 gout patients and 40 controls using real-time PCR. Urate levels were measured by a colorimetric method, and XDH levels by ELISA. Genotypic distributions were analyzed, and associations were estimated using logistic regression models.
RESULTS: Urate and XDH levels were significantly higher in patients than in controls (p = 0.0004 and p = 0.010, respectively). For the rs17323225 variant, the TT genotype was associated with an increased risk of gout compared to controls (OR = 3.69, 95% CI = 1.06-12.8, p = 0.04). Furthermore, individuals with the TT genotype had higher urate and XDH levels than those with other genotypes (p < 0.001 and p = 0.043, respectively).
CONCLUSION: The rs17323225 variant of the XDH gene may be a genetic risk factor for gout in the Mexican population. These findings suggest that XDH genetic variability contributes to urate metabolism dysregulation and could aid in identifying individuals at higher genetic risk for gout, supporting personalized prevention and treatment approaches. Key Points • Xanthine dehydrogenase (XDH) is an enzyme that catalyzes the sequential conversion of hypoxanthine to xanthine, and of xanthine to urate. • The XDH rs17323225 TT genotype is significantly associated with higher levels of serum urate and XDH, suggesting a functional role in urate biosynthesis. • XDH genotyping may help identify individuals at higher risk of gout and guide tailored urate-lowering or xanthine dehydrogenase-targeted therapies.