संक्रामक रोग और चिकित्सा जर्नल

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

Abstract

Farah Thamer Hasan and Hassan Mohammad Naif

Background: IL-18 gene polymorphism 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) of were distributed variably in both patients and controls: CC, CA, and AA with frequencies 41 (82%), 3 (6%), and 6 (12%), in patients while were 44 (88%), 5 (10%), and 1 (2%) in the controls, respectively. The homozygous AA 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-18-317G/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 and alleles (G and C) distribution between patients and controls. No significant differences of the allele frequencies of both G and C alleles between patients and controls (OR=0.863, 95%CI=0.4485-1.7516). A serum level of IL-18 was found to be significantly higher in HBV-infected patients compared to the control group. IL- 18 levels decreased significantly by different genotypes of both SNPs but were consistently associated with 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 -307 genotypes had no clear impact on the disease and its role as a protective factor needs further investigation. In contrast, the down regulation of the circulating levels of IL-18 in patients was associated with the -317 and -607 genotypes.