Disheveled EGL-10 and pleckstrin domain-containing 5 rs1012068 T/G gene polymorphism among Egyptian chronic HCV-infected patients: disease progression and related complications

Abstract

Hepatitis C virus (HCV) infection related complications including fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are influenced by host genetic factors. Identification of emerging host genetic variations is of promising value. Disheveled EGL-10 and pleckstrin domain-containing 5 (DEPDC5) rs1012068 T/G gene polymorphism has been implicated in liver disease. This study aimed to assess DEPDC5 rs1012068 T/G gene polymorphism with disease progression and related complications among Egyptian patients with chronic HCV infection. Sixty chronic HCV-infected patients and 60 apparently healthy controls were recruited in this study. Patients were classified into 20 with liver fibrosis, 20 with liver cirrhosis and 20 with HCC; all recruited from Outpatients Clinic and Tropical Medicine Inpatient Department, Faculty of Medicine, Beni-Suef University Hospital. DEPDC5 rs1012068 T/G gene polymorphism was assayed by real time-polymerase chain reaction (RT-PCR) TaqMan allelic discrimination. DEPDC5 rs1012068 GG genotype and G allele variants showed statistically significant higher frequency among patients with liver fibrosis when compared to controls (OR (95% CI) 10.500 (2.086 – 52.851), P= 0.004 and 0.388 (0.155 – 0.971), P= 0.011), respectively. DEPDC5 rs1012068G allele variant showed statistically significant higher frequency among patients with liver fibrosis when compared to HCC patients (OR (95% CI) 3.316 (1.286 – 8.550), P= 0.012) and to both HCC and cirrhosis patients (OR (95% CI) 2.579 (1.187-5.645), P= 0.016). In conclusion, our results suggest that DEPDC5 rs1012068 G allele could be considered genetic risk allele for liver fibrosis and disease progression among Egyptian patients with chronic HCV infection.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

“…No relevant case-control studies were identifed based on the alternative polymorphism IDs for rs1012068 (rs56511012, rs58339834, rs386510025) or for rs5998152 (rs61578881, rs8143107). A total of 11 studies [12][13][14][15][16][17][18][19][20][21][22] investigated rs1012068, and 3 studies [12,15,23] investigated rs5998152. Te distribution of genotypes in controls was consistent with Hardy-Weinberg equilibrium (HWE).…”

“…rs1012068 and HCC Risk. As shown in Table 2 and Figure S1, a meta-analysis based on a population of 2,609 cases and 8,171 in 11 studies [12][13][14][15][16][17][18][19][20][21][22] revealed that the rs1012068 polymorphism did not signifcantly increase HCC risk in total under the allelic model (OR � 1.32, 95% CI � 1.04-1.67, P � 0.02); the recessive model (OR � 1.42, 95% CI � 0.96-2.10, P � 0.08); the dominant model (OR � 1.43, 95% CI � 1.09-1.87, P � 0.01); the homozygous model (OR � 1.61, 95% CI � 1.01-2.57, P � 0.05); or the heterozygous model (OR � 1.39, 95% CI � 1.09-1.79, P � 0.009).…”

“…A meta-analysis based on ethnicity for the subgroup of 2,297 Asian cases and 4,801 Asian controls in 8 studies [12,[14][15][16][17][18][19][20] showed that the rs1012068 polymorphism signifcantly increased HCC risk in Asians (Table 2; Figure 2) under the allelic model (OR � 1.56, 95% CI � 1. 22 Ten, we conducted a meta-analysis based on the etiology of HCC, in which both cases and controls were chronically infected with HBV. Results for the subgroup of 936 cases and 1,021 controls in 3 studies [14,16,19] showed that the rs1012068 polymorphism signifcantly increased HCC risk in individuals with chronic HBV infection (Table 2; Figure 3) under the allelic model (OR � 1.34, 95% CI � 1.16-1.54, P < 0.001); the recessive model (OR � 1.62, 95% CI � 1.16-2.26, P � 0.004); the dominant model (OR � 1.39, 95% CI � 1.16-1.66, P < 0.001); the homozygous model (OR � 1.82, 95% CI � 1.29-2.56, P < 0.001); and the heterozygous model (OR � 1.31, 95% CI � 1.08-1.59, P � 0.005).…”

“…Next, a meta-analysis was conducted based on the etiology of HCC, in which both cases and controls were chronically infected with HCV. Results for the subgroup of 1,673 cases and 7,150 controls in 8 studies [12,13,15,17,18,[20][21][22] showed that the rs1012068 polymorphism did not signifcantly increase HCC risk in individuals with chronic HCV infection (Table 2; Figure S2) under the allelic model (OR � 1.46, 95% CI � 1.03-2.05, P � 0.03); the recessive model (OR � 1.63, 95% CI � 1.00-2.66, P � 0.05); the dominant model (OR � 1.56, 95% CI � 1.04-2.34, P � 0.03); the homozygous model (OR � 1.91, 95% CI � 0.99-3.65, P � 0.05); and the heterozygous model (OR � 1.48, 95% CI � 1.02-2.16, P � 0.04). 2 and Figure 4, a meta-analysis based on a population of 411 cases and 1,448 controls in 3 studies [12,15,23] revealed that the rs5998152 polymorphism was signifcantly associated with HCC risk in Asians with chronic HCV infection under the allelic model (OR � 1.56, 95% CI � 1.05-2.33, P � 0.03); the dominant model (OR � 1.82, 95% CI � 1.44-2.30, P < 0.001); and the heterozygous model (OR � 1.82, 95% CI � 1.43-2.31, P < 0.001); but not under the recessive model (OR � 1.32, 95% CI � 0.77-2.26, P � 0.31); or the homozygous dominant model (OR � 1.62, 95% CI � 0.93-2.82, P � 0.09).…”

“…In addition to these associations between DEPDC5 and various diseases, polymorphisms in the DEPDC5 gene have been linked to the risk of HCC [12][13][14][15][16][17][18][19][20][21][22][23]. A genome-wide association study frst demonstrated that the DEPDC5 variant rs1012068 could increase HCC risk in individuals with chronic HCV infection [12], and this relationship was replicated in several studies [15,18,20].…”