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

Abstract

BackgroundVesicoureteral reflux (VUR) is a common childhood disorder that is characterized by the abnormal movement of urine from the bladder into the ureters or kidneys.ObjectivesThe 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 MethodsThe 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.ResultsA 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.ConclusionsThe 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.

Interleukin‐10‐1082A/G polymorphism is associated with renal parenchymal damage in congenital anomalies of the kidney and urinary tract

“…have presented the haplotype, containing the G‐allele of ‐1082 SNP in a homozygous state (GCC/GCC) as a risk factor for renal scarring among Turkish patients with VUR . Another recent study on 124 VUR patients from Southeast Iran, has shown that all of the genotypes containing variant G‐allele (AG, GG, and AG + GG) of ‐108A/G SNP, highly increased the risk of the disease (OR = 12.6, 95% CI = 2.9–113.9; P = 0.00003; OR = 15, 95% CI = 0.6–117.31; P = 0.06; OR = 12.62, 95% CI = 2.93–114.53; P = 0.00003, respectively) . However, the last study does not explore the role of ‐1082A/G polymorphism for the reflux nephropathy.…”

“…However, currently, there are just two associative studies that have investigated the role of -1082A/G polymorphism for genetic risk of VUR. 14,15 To our knowledge, the role of -1082A/G polymorphism in the IL10 gene in other malformations from CAKUT spectrum has not been previously explored.…”

“…14 Another recent study on 124 VUR patients from Southeast Iran, has shown that all of the genotypes containing variant G-allele (AG, GG, and AG + GG) of -108A/G SNP, highly increased the risk of the disease (OR = 12.6, 95% CI = 2.9-113.9; P = 0.00003; OR = 15, 95% CI = 0.6-117.31; P = 0.06; OR = 12.62, 95% CI = 2.93-114.53; P = 0.00003, respectively). 15 However, the last study does not explore the role of -1082A/G polymorphism for the reflux nephropathy. Our present study is the first report about the role of IL10 -1082A/G SNP in CAKUT patients with respect to parenchymal damage/reduction.…”

“…In regard to the above, the functional polymorphism ‐1082A/G in IL10 may have a prominent role for the genetic predisposition to the malformations from CAKUT spectrum. However, currently, there are just two associative studies that have investigated the role of ‐1082A/G polymorphism for genetic risk of VUR . To our knowledge, the role of ‐1082A/G polymorphism in the IL10 gene in other malformations from CAKUT spectrum has not been previously explored.…”