Single nucleotide polymorphism of the promotor region of Interleukin-10 gene did not show significant association with spontaneous clearance of hepatitis C virus infection in Egyptian patients

Abstract

Introduction: Accurate etiologies of spontaneous clearance of HCV infection are hard to be clarified. However, it is proposed that genetically determined interleukin-10 (IL-10) changes play an important function in HCV elimination. Individuals who are homozygous for IL-10 gene promoter region 1082 (G/A; rs1800896) genotype AA have significantly lower levels of plasma IL-10 levels with better capability of spontaneous viral clearance (SVC); while those with GG genotype have two folds greater level of IL-10 than GA or AA persons, leading to diminished capability of SVC. Aims: The study aimed at identifying the IL-10 gene promoter region 1082 (G/A; rs1800896) polymorphism as a possible predictor of SVC of HCV infection in Egyptian patients and its relation with the viral load and the degree of liver injury in chronic hepatitis C (CHC) patients. Methods: The study was conducted on two groups; group I which included 100 cases of CHC defined as detectable anti-HCV antibodies and detectable serum HCV RNA for ≥ 6 months and group II which included 50 cases of SVC defined as detectable anti-HCV antibodies for ≥ 6 months and undetectable HCV RNA in two consecutive tests, 3 months apart, without previous antiviral therapies. HCV antibody testing was done using 4th generation enzyme-linked immuno sorbent assay (ELISA) technique. HCV-RNA quantification was done using polymerase chain reaction (PCR) technique. Detection of IL10 1082 (G/A; rs1800896) polymorphism was done by PCR restriction fragment length polymorphism (RFLP) technique. Complete blood count (CBC); serum albumin, serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), serum creatinine and HBsAg, were done for all participants. Child-Turcotte-Pugh (CTP) class & FIB4 score were calculated. Abdominal ultra-sonography (US) and contrast enhanced computed tomography (CT) of the abdomen were done for all participants. Results: In group I, the age was 53.6±11.2 years old, males represented 51% and females represented 49%. In group II, the age was 52.8±8.6 years old, males represented 48% and females represented 52%. No significant differences were found regarding age and gender (p=0.658, 0.729 respectively). Group I showed significantly higher frequency of hepatomegaly, splenomegaly & liver cirrhosis (p < 0.001) and significantly lower platelet count (PLC) (183.5±61.1 versus 220.3±67.2 ×109/L, p=0.006). Group I showed significantly higher ALT, AST & FIB4 score (p <0.001, 0.002, <0.001 respectively). Group I had median viral load of 555640 IU/mL. Applying Hardy Weinberg (HW) equation, IL10 1082 (G/A; rs1800896) genotypes in both groups were in HW equilibrium (HW p=0.845&0.861 respectively). In Group I, genotype AA represented 72%, AG represented 26% & GG represented 2%, while in Group II, genotype AA represented 62%, AG represented 34% & GG represented 4% ,with insignificant differences between both groups (p=0.272, 0.415 & 0.216 respectively). In Group I, no significant differences regarding HCV RNA load ,CTP class, PLC , FIB4 score ,were found between the three genotypes (p=0.191, 0.086, 0.754,0.829, 0.187 respectively). Multivariate logistic regression analysis showed that IL10 1082 (G/A; rs1800896) genotypes was not a significant predictor of SVC of HCV infection in Egyptian patients (p=0.216.OR=1.322, 95% CI=0.849-2.058). Conclusion: Single nucleotide polymorphism of the promoter region of the IL-10 gene, 1082 (G/A; rs1800896), did not show significant association with the spontaneous clearance of hepatitis C virus infection in Egyptian patients. In chronic hepatitis C patients, this SNP had no significant association with the serum HCV viral load, CTP class, PLC or FIB4 score.