rs1800796 of the IL6 gene is associated with increased risk for anti-tuberculosis drug-induced hepatotoxicity in Chinese Han children

Li, Yingjia; Tang, Haijing; Qi, Hui; Shen, Chen; Sun, Lin; Li, Jieqiong; Xu, Fang; Jiao, Weiwei; Yang, Xu; Shen, Adong

doi:10.1016/j.tube.2018.05.011

Cited by 7 publications

(5 citation statements)

References 47 publications

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“…To the best of our knowledge, the association between polymorphism of rs206860 and hypertension was not widely reported. rs206860 was investigated in the studies of advanced liver disease [32] and anti-tuberculosis drug-induced hepatotoxicity [33]. As far as we know, other SNPs were not directly reported regarding association between heterogeneity of SNPs and hypertension.…”

Section: Discussionmentioning

confidence: 99%

Association between Serum Urate and Risk of Hypertension in Menopausal Women with XDH Gene

Lee

et al. 2019

JCM

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Elevated serum urate (sUA) concentrations have been associated with an increased risk of hypertension. We aimed to examine the association of sUA concentration on the risk of hypertension in pre- and post-menopausal women and investigated the association between the polymorphism of the xanthine dehydrogenase gene and the risk of hypertension. Among 7294 women, 1415 premenopausal and 5879 postmenopausal women were recruited. Anthropometric parameters as risk factors of hypertension were identify by logistic regression models. In addition, we investigated an association between xanthine dehydrogenase gene and sUA and their combined associations on the risk of hypertension. Body mass index (BMI) and waist circumference (WC) were significantly increased in accordance to the increase of sUA levels (p < 0.001). Multivariate logistic regression analysis showed postmenopausal women with a high sUA and high BMI were 3.18 times more likely to have hypertension than in those with normal and lower sUA (Odds ratio: 3.18, 95% confidence interval: 2.54–3.96). Postmenopausal women with a high WC were 1.62 times more likely to have hypertension than in those with normal and lower sUA. Subjects with the AG genotype of rs206860 was found to be at lower risk of hypertension (odd ratio: 0.287, 95% confidence interval: 0.091–0.905, p = 0.033). This cross-sectional study indicated a high sUA is associated with a higher risk of hypertension in postmenopausal women. Further well-designed prospective studies in other populations are warranted to validate our results.

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Section: Discussionmentioning

confidence: 99%

Association between Serum Urate and Risk of Hypertension in Menopausal Women with XDH Gene

Lee

et al. 2019

JCM

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“…IL-6 is a proinflammatory cytokine secreted upon infection by various cells such as T lymphocytes, B lymphocytes, monocytes and identified by this study as a possible genetic risk factor of ANE. In chronic infectious diseases, rs1800796G allele, GG genotype or G-containing haplotype is reportedly associated with a decreased risk of tuberculosis (Zhang et al, 2012;Wang et al, 2017), increased risk of anti-tuberculosis drug-induced hepatotoxicity (Li et al, 2018), decreased prevalence of chronic human hepatitis B virus (HBV) infection (Zhang et al, 2015;Li et al, 2021), decreased chance of sustained viral response to antiviral therapy against chronic hepatitis C virus (HCV) infection (Yee et al, 2009;Sghaier et al, 2017b), and a decreased risk of progression from HCV infection to hepatocellular carcinoma (Sghaier et al, 2017b). In acute infectious diseases, rs1800796G allele is reportedly associated with an increased risk of sepsis in chronic renal disease (Panayides et al, 2015) and increased risk of post-traumatic osteomyelitis (Jiang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Association of IL6 and IL10 gene promotor polymorphisms with susceptibility to acute necrotizing encephalopathy

et al. 2023

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ObjectiveAcute necrotizing encephalopathy (ANE) is a severe complication of infectious diseases affecting the brain and systemic organs. The main pathogenesis is cytokine storm, in which interleukin-6 (IL-6) and interleukin-10 (IL-10) are candidates for key cytokines. To further elucidate their roles in the etiology and pathogenesis of ANE, we studied polymorphisms in the promotor regions of the IL6 and IL10 genes by genetic and functional analyses.MethodsWe first conducted a case–control association study of four IL6 and three IL10 polymorphisms. We genotyped 31 Japanese ANE cases and compared the results with those of approximately 200 Japanese controls. For the two polymorphisms showing a possible association, we next studied whether the polymorphisms alter the production of IL-6 or IL-10 by lymphoblasts upon phorbol 12-myristate 13-acetate (PMA) stimulation.ResultsThe frequencies of IL6 rs1800796G allele and IL10 rs1800871/rs1800872 CC/CC diplotype were significantly higher in ANE cases than in controls. The IL10 CC/CC diplotype was associated with low IL-10 production, whereas the IL6 GG genotype was not associated with IL-6 production.ConclusionIL10 rs1800871/rs1800872 CC/CC diplotype may predispose Japanese children to ANE by altering IL-10 production in the early phase of infection. Etio-pathogenetic significance of IL6 rs1800796G remains to be elucidated.

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“…In a trans-ethnic meta-analysis from Nicoletti et al, CYP2E1 was not associated with AT-DILI [ 46 ]. For IL6 association with AT-DILI, the few results reported are not conclusive [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the liver, IL6 is a major inducer of the acute phase response after infection, simultaneously improving hepatic regeneration and repair, but in more chronic exposure, it can actually contribute to liver damage [ 25 , 26 , 27 ]. IL6 gene upstream SNPs rs1800796 and rs1800797 have been associated with susceptibility to liver diseases though the impact and risk genotypes varied with ethnicity [ 28 , 29 ]. Although NAT2 function is specifically related to INH-DILI, CYP2E1, GSTs, BSEP, and IL6 have broad-range roles and may also be implicated in the hepatotoxic effect of other antituberculosis drugs.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers

Cavaco¹,

Alcobia

Oliveiros

et al. 2022

JPM

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Drug-induced liver injury (DILI) is an unpredictable and feared side effect of antituberculosis treatment (AT). The present study aimed to identify clinical and genetic variables associated with susceptibility to AT-associated hepatotoxicity in patients with pulmonary tuberculosis treated with a standard protocol. Of 233 patients enrolled, 90% prospectively, 103 developed liver injury: 37 with mild and 66 with severe phenotype (DILI). All patients with mild hepatitis had a RUCAM score ≥ 4 and all patients with DILI had a RUCAM score ≥ 6. Eight clinical variables and variants in six candidate genes were assessed. A logistic multivariate regression analysis identified four risk factors for AT-DILI: age ≥ 55 years (OR:3.67; 95% CI:1.82–7.41; p < 0.001), concomitant medication with other hepatotoxic drugs (OR:2.54; 95% CI:1.23–5.26; p = 0.012), NAT2 slow acetylator status (OR:2.46; 95% CI:1.25–4.84; p = 0.009), and carriers of p.Val444Ala variant for ABCB11 gene (OR:2.06; 95%CI:1.02–4.17; p = 0.044). The statistical model explains 24.9% of the susceptibility to AT-DILI, with an 8.9 times difference between patients in the highest and in the lowest quartiles of risk scores. This study sustains the complex architecture of AT-DILI. Prospective studies should evaluate the benefit of NAT2 and ABCB11 genotyping in AT personalization, particularly in patients over 55 years.

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rs1800796 of the IL6 gene is associated with increased risk for anti-tuberculosis drug-induced hepatotoxicity in Chinese Han children

Cited by 7 publications

References 47 publications

Association between Serum Urate and Risk of Hypertension in Menopausal Women with XDH Gene

Association between Serum Urate and Risk of Hypertension in Menopausal Women with XDH Gene

Association of IL6 and IL10 gene promotor polymorphisms with susceptibility to acute necrotizing encephalopathy

Clinical and Genetic Risk Factors for Drug-Induced Liver Injury Associated with Anti-Tuberculosis Treatment—A Study from Patients of Portuguese Health Centers

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