Analysis of the IL-10, IL-12, and TNF-α Gene Polymorphisms in Patients With Vesicoureteral Reflux Among the Southeast Iranian Population

BACKGROUND Vesicoureteral reflux (VUR) is a common childhood disorder that is characterized by the abnormal movement of urine from the bladder into the ureters or kidneys. OBJECTIVES The aim of this study was to determine whether the genetic polymorphisms of the IL-10, IL-12, and TNF-α genes are involved in the development of VUR. PATIENTS AND METHODS The tetra amplification mutation refractory system-polymerase chain reaction (Tetra-ARMS PCR) was applied to analyze the four polymorphic sites of the IL-10AG-1082, IL-10CA597, IL-12CA1188, and TNF308GA genes in 124 VUR children and 110 healthy controls. RESULTS A significant, highly increased risk of VUR disease was found for the CA, AA, and combined genotypes of IL-10CA597 (OR = 5.2, 95% CL: 1.80 - 18.25; P = 0.0006, OR = 9.1, 95% CL: 1.11 - 122.75; P = 0.02, OR = 5.3, 95% CL: 1.82 - 18.61; P = 0.00052, respectively); the AG, GG, and AG + GG genotypes of IL-10AG-1082 (OR = 12.8, 95% CL; 2.9 - 113.9; P = 0.00003, OR = 12.62, 95% CL: 2.93 - 114.53; P = 0.00003, respectively); and the AA genotype of IL-12 (AA, OR = 0.19, 95% CL: 0.5 - 0.55; P = 0.0006). The frequency of the C allele in both IL-10CA and IL-12CA was greater in patients with VUR than in the healthy controls. No association was found between TNF308GA and the risk of VUR. CONCLUSIONS The results demonstrated significant associations between the IL-10 (AG-1089, IL-10CA) and IL-12 (AA) gene polymorphisms and a highly increased risk of VUR.