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

Abstract

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.

Association of interleukin-18 genotypes (−607C > A) and (−137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma

“…When the association of the genotypes with HBV progression and subsequent HCC risk was studied, the IL-18 (-607) CA genotype was found to be a signi cant protective factor in Hepatitis B virus disease progression. This observation differed from the study conducted by Hasan et.al [40] who found no signi cant difference for CA genotype of IL-18(-607) in HBV infection. A study by Chang et al showed an association of the CA and CC genotypes of IL-18(− 607) with a signi cant decrease in the risk of renal cell carcinoma [RCC] compared with the AA genotype [41].…”

A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18, IL17A, and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease

“…The studied Chagas disease patient population presented a balanced gender composition, predominance of whites and a median age of 50 (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) The entire study population was in Hardy-Weinberg equilibrium (HWE) (Supplementary Table 2). The genotype frequencies were also in HWE in whites and non-whites (Supplementary Table 2).…”

“…Variants of these two sites can not only affect IL18 transcription but also IFNg expression (58). The −607 A allele and AA genotype have been associated with lower IL18 transcriptional rate and/or protein levels than the C allele and CC genotype in different clinical and physiological settings (59)(60)(61)(62)(63), whereas the haplotype C-607/G-137 is associated with higher expression of IL18. Our analyses, however, did not identify a significant impact of IL18 −607 or IL18 −137 alleles/ genotypes on the T. cruzi parasitemic status.…”

“…Unlike these studies, however, our data did not reveal significant associations between IL18 levels and any of the IL18 −607 or IL18 −137 genotypes/alleles. Such differences may rely on the nature and size of the studied populations (55-101 patients), including other diseases, and/or the nature the biological samples and/or experimental conditions, including plasma and mucosal biopsies and peripheral blood cells under mitogen stimuli (58)(59)(60)(61)(62)(63). The lack of association between IL18 serum levels and IL18 −607 C>A or IL18 −137 C>G genotypes/ alleles observed in our study does not allow a straight association between the mentioned cardiac findings and IL18 serum levels.…”

Polymorphism in the Promoter Region of the IL18 Gene and the Association With Severity on Paracoccidioidomycosis

“…The -607 C-allele/CC-genotype carriage has been associated with higher levels of IL-18 in the serum and/or of mRNA expression (50,66,(68)(69)(70). In our study, we found higher Callele carriage on patients with the UC form of PCM (73.5%), whereas the AF and MC groups (with 46.2 and 51.1% of C-allele carriage, respectively) had already been reported to have higher serum IL-18 levels than those from the former group (19,20).…”