Association between inflammatory-response gene polymorphisms and risk of acute kidney injury in children

Abstract

In the present study, we investigated the association of 12 polymorphisms in six inflammatory-response genes (TNF, IL6, IL10, IL18, NFKB1 and NFKBIA) with risk of acute kidney injury (AKI) in children. The polymorphisms were genotyped in 1138 children with AKI and 1382 non-AKI controls. Logistic regression analysis was performed to calculate the odds ratio for estimating the risk association. After accounting for Bonferroni correction and adjustment for potential confounders, significant association was observed for NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms (P < 0.004). All three polymorphisms were associated with a reduced risk of AKI. For rs28362491 polymorphism, the OR for ID vs. II comparison was 0.75 (95% CI = 0.58–0.83) while that for DD vs. II was 0.44 (95% CI = 0.30–0.67). For rs2233406 polymorphism, the CT vs. CC comparison showed an OR of 0.90 (95% CI = 0.39–0.99), while the TT vs. CC comparison showed an OR of 0.43 (95% CI = 0.33–0.80). For rs696 polymorphism, the OR for AG vs. AA comparison was 0.71 (95% CI = 0.43–0.89), while the GG vs. AA comparison showed an OR of 0.39 (95% CI = 0.21–0.71). In conclusion, NFKB1 rs28362491, NFKBIA rs2233406 and NFKBIA rs696 polymorphisms may serve as biomarkers for predicting risk of AKI in children.

Ethnicity-Stratified Analysis of the Association between TNF-α Genetic Polymorphisms and Acute Kidney Injury: A Systematic Review and Meta-Analysis

“…Within all of the included studies, there were 7 studies related to TNF- α rs1800629 polymorphism and 3 studies related to TNF- α rs1799964 polymorphism. Regarding the TNF- α rs1800629 studies, the subjects in 5 studies [ 14 , 15 , 19 – 21 ] were Caucasians and the subjects in the other 2 were Asians [ 16 , 17 ]. Regarding the TNF- α rs1799964 studies, all the 3 included studies were conducted in the Asian population [ 16 – 18 ].…”

“…Regarding the TNF- α rs1800629 studies, the subjects in 5 studies [ 14 , 15 , 19 – 21 ] were Caucasians and the subjects in the other 2 were Asians [ 16 , 17 ]. Regarding the TNF- α rs1799964 studies, all the 3 included studies were conducted in the Asian population [ 16 – 18 ]. All the included studies were assessed as high quality (NOS score ≥ 6, see Additional file 2 ), and the genotyping distributions were genetically balanced ( P > 0.05).…”

“…One of the reasons is that the studies conducted in Caucasians mainly included critically ill patients from the intensive care unit with severe infection [ 14 , 19 – 21 ] or underwent cardiac surgery [ 15 ]. The patients included in Asian studies underwent coronary artery intervention [ 17 ] or were pediatric patients [ 16 ], with a lower incidence of comorbidity or better baseline renal function. Another possible explanation is that the distribution of TNF- α rs1800629 alleles is population dependent.…”

“…Some studies had analyzed the association between two TNF- α promoter SNPs (rs1800629 and rs1799964) and AKI susceptibility [ 14 – 18 ]. Dalboni et al [ 14 ] and McBride et al [ 14 , 15 ] conducted studies in Caucasians and found that TNF- α rs1800629 had no association with susceptibility to AKI, while studies conducted in Asians indicated that both TNF- α rs1800629 and rs1799964 had a positive association with AKI [ 16 , 18 ].…”

Association between Kidney Injury Molecule-1 Gene Polymorphism and Acute Kidney Injury among the Lebanese Patients

“…The variability in the prediction of adverse kidney-related outcomes still has no significant explanation. In recent years, the role of genetic single nucleotide polymorphisms as possible determinants of adverse outcomes in AKI patients and the severity of the disease has been the interest of many studies (He et al, 2018;Leung et al, 2009;Susantitaphong et al, 2013). Due to known limitations in creatinine and urine output tests, the "gold standard" of AKI biomarkers, new specific, early, and more sensitive biomarkers are needed.…”