Interleukin-18 promoter polymorphisms and the disease progression of Hepatitis B virus-related liver disease

Migita, Kiyoshi; Sawakami-Kobayashi, Kazumi; Maeda, Yümi; Nakao, Kazuwa; Kondoh, Susumu; Sugiura, Mika; Kawasumi, Ryoko; Segawa, Osamu; Tajima, Hideji; Machida, Masayuki; Nakamura, Minoru; Yano, Koji; Abiru, Seigo; Kawasaki, Eiji; Yatsuhashi, Hiroshi; Eguchi, Katsumi; Ishibashi, Hiromi

doi:10.1016/j.trsl.2008.11.008

Cited by 27 publications

(29 citation statements)

References 25 publications

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“…A further two studies3839 were excluded because they included either patients with only liver cirrhosis or an aggregated patient population with HCC or liver cirrhosis. In the end, 8 studies1213141516171819 were included in the final meta-analysis based on our search strategy and inclusion criteria (Table 1). Of these 8 studies, all1213141516171819 evaluated the association between the -137 polymorphism and HCC risk (1,318 cases, 2,254 controls), while 7 studies12141516171819 evaluated the association between the -607 polymorphism and HCC risk (1,262 cases, 1,696 controls).…”

Section: Resultsmentioning

confidence: 99%

“…Meta-analysis of 7 studies12131416171819 involving 1,206 Asian cases and 2,052 Asian controls showed no evidence of a significant association between the -137 polymorphism and HCC risk for any of the five genetic models (Table 3): allelic, OR 1.01, 95% CI 0.71–1.43, P = 0.97; recessive model, OR 1.08, 95% CI 0.68–1.70, P = 0.75; dominant, OR 0.99, 95% CI 0.62–1.57, P = 0.96; homozygous, OR 1.09, 95% CI 0.69–1.72, P = 0.73; heterozygous, OR 0.98, 95% CI 0.61–1.56, P = 0.92. Similarly, no evidence of an association was identified in meta-analysis of 4 studies14171819 involving 832 Chinese cases and 1,151 Chinese controls (Table 3): allelic, OR 0.87, 95% CI 0.54–1.39, P = 0.56; recessive, OR 0.89, 95% CI 0.49–1.65, P = 0.72; dominant, OR 0.86, 95% CI 0.45–1.66, P = 0.66; homozygous, OR 0.80, 95% CI 0.43–1.48, P = 0.48; heterozygous, OR 0.85, 95% CI 0.44–1.66, P = 0.64.…”

Section: Resultsmentioning

confidence: 99%

“…Lastly, we meta-analyzed the subgroup of 978 cases and 1,752 controls in 6 studies121316171819 in which the numbers of cases with HBV-related HCC were reported. The other two studies1415 did not report results based on HCC etiology.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, numerous case-control studies1213141516171819 have investigated whether polymorphisms at position -137 (rs187238) and -607 (rs1946518) within the IL-18 promoter influence risk of HCC. Results have been inconclusive and contradictory, prompting us to perform the first comprehensive meta-analysis of all available evidence on these potential associations.…”

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confidence: 99%

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Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

Zhu

Zhao

et al. 2016

Sci Rep

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This study meta-analyzed the literature on possible association of polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 (IL-18) promoter with risk of hepatocellular carcinoma (HCC). The analysis included 8 case-control studies on the -137 polymorphism (1,318 cases, 2,254 controls) and 7 case-control studies on the -607 polymorphism (1,262 cases, 1,696 controls). None of the five genetic models suggested a significant association between the -137 polymorphism and HCC risk: allelic model, OR 0.99, 95% CI 0.74–1.34, P = 0.97; recessive model, OR 0.98, 95% CI 0.65–1.46, P = 0.91; dominant model, OR 1.35, 95% CI 0.73–2.52, P = 0.34; homozygous model, OR 0.99, 95% CI 0.65–1.49, P = 0.95; heterozygous model, OR 0.99, 95% CI 0.66–1.48, P = 0.94. Similar results were obtained in subgroup analyses of Asian patients, Chinese patients, or patients with hepatitis B virus (HBV)-related HCC. Similar results were also obtained for the -607 polymorphism across the entire study population as well as in the three subgroups. The available evidence suggests no significant association of the -137 or -607 polymorphisms with risk of HCC in general or specifically of HBV-related HCC. These conclusions should be verified in large, well-designed studies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

Zhu

Zhao

et al. 2016

Sci Rep

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“…Moreover, the IL-18-607 SNP with AA genotype was accompanied by inhibition of HBV DNA replication [20]. In addition, Migita et al [22] in a study comprised of 204 chronically HBV-infected patients; suggested that IL-18 -607 and -137 had differential outcomes on HBV infection, where they found that these SNPs are significantly higher in inactive HBV carriers compared to those with chronic progressive liver disease. Moreover, Hirankarn et al [23] found that A/A genotype of IL-18-607 SNP (rs1946518) can be used as a new genetic marker in Thai population for prediction of chronic hepatitis B development.…”

Section: Discussionmentioning

confidence: 99%

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

Hasan¹,

Naif²

2017

J Infect Dis Med

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Background: IL-18 gene polymorphisms is shown to be involved in various diseases. This study examines the influence of IL-18 gene polymorphism on the natural course of Hepatitis B Virus (HBV) infection together with the impact of serum levels in Iraqi population for the first time.Methods: A total of 55 patients and similar numbers of healthy controls were recruited in this study. Gene polymorphisms at positions -607C/A and -137G/C of IL-18 were examined using the allele-specific polymerase chain reaction (PCR). Serum levels of IL-18 were determined by an ELISA kit.Results: Three genotypes of IL-18-607C/A (rs1946518) were observed and distributed variably in both patients and controls: CC, CA, and AA with frequencies 41 (82%), 3 (6%), and 6 (12%), in patients and in 44 (88%), 5 (10%), and 1 (2%) in the controls, respectively. The homozygous -607AA mutant genotype, A and C allele frequencies were significantly higher (p=0.043) in patients than the healthy control group (A: 15% and 7%, p=0.04 and C: 85% and 93%, p=0.04, respectively) (OR=2.3445, 95%CI=0.9121-6.0269). The effect of treatment against HBV on genotype and allele frequencies compared with untreated patients revealed that CC and AA genotypes were significantly higher (p=0.04) in treated than untreated patients mirrored results obtained in patients and controls. Three genotypes of IL-18-137G/C (rs187238) were observed in both patients and healthy controls: GG, GC, and CC that appeared in 30 (60%), 18 (36%), and 2 (4%) of HBV infected patients and in 32 (64%), 16 (32%), and 2 (4%) of the control group, respectively. No significant genotype or alleles (G and C) frequencies observed between patients and controls (OR=0.863, 95%CI=0.4485-1.7516). Serum levels of IL-18 was found to be significantly higher in HBV-infected patients compared to the control group. IL-18 levels decreased significantly by various genotypes of both SNPs and this was consistently associated with the mutant genotypes of -137 SNP.Conclusion: IL-18-607AA mutant genotype and C and A alleles were significantly associated with a high risk to HBV infection in Iraqi population, however, the -137 genotypes had no clear impact on the disease and its role as a protective factor needs further investigation. In contrast, the downregulation of the circulating levels of IL-18 in patients was associated with the -137 and -607 mutant genotypes.

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Association of genetic variants in the interleukin‐18 gene promoter with risk of hepatocellular carcinoma and metastasis in patients with hepatitis C virus infection

2018

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Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, characterized by high vascularization and rapid tumor progression. The current case-control study aimed to analyze the influence of -607C/A and -137G/C polymorphisms in the interleukin-18 (IL-18) promoter on the risk of HCC occurrence and metastasis in Egyptian patients infected with hepatitis C virus (HCV). Both genetic variations were genotyped in 279 subjects including HCV patients with and without HCC and unrelated healthy subjects, using the allele-specific polymerase chain reaction (AS-PCR) method. The relationship between clinico-laboratory parameters including serum level of alpha-fetoprotein (AFP) and these polymorphisms was evaluated in HCC patients. The IL-18-607A allele and AA genotype were significantly related to a higher risk of developing HCC when comparing patients with HCC and controls, and were significantly related to a higher risk of metastasis when comparing metastatic and nonmetastatic groups in the Egyptian patients. In contrast, the IL18-137C allele and GC genotype were significantly related to a lower risk of developing HCC when comparing patients with HCC and controls, and HCV patients with and without HCC. A significant association was found between multinodular HCC and IL-18-607AA genotype, while, uninodular HCC was significantly associated with IL-18-137GG genotype. In addition, IL18-607AA and -137GG genotypes showed significant association with higher level of serum AFP. The detection of polymorphisms in the IL-18 promoter, in a combination with an evaluation of level of serum AFP, could be used as a molecular biomarker in the early diagnosis of HCC, which would aid the early management of the disease, thus decreasing the rate of mortality of this disease. © 2018 IUBMB Life, 70(2):165-174, 2018.

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Interleukin-18 promoter polymorphisms and the disease progression of Hepatitis B virus-related liver disease

Cited by 27 publications

References 25 publications

Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

Association of genetic variants in the interleukin‐18 gene promoter with risk of hepatocellular carcinoma and metastasis in patients with hepatitis C virus infection

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