Association of Adiponutrin/Patatin Like Phospholipase 3 (PNPLA3) I148M Gene Variant with Chronic Hepatitis C in Egyptian Children

Background: Chronic hepatitis C (CHC) represents a leading cause of liver-related mortality worldwide. The patatin-like phospholipase domain-containing 3 gene (PNPLA3/adiponutrin) rs738409 (I148M) single-nucleotide polymorphism (SNP) has been reported to be linked with the severity and progression of liver fat content and liver fibrosis in CHC among different racial groups. Such reports are lacking in CHC Egyptian children.

Aim of Study: To evaluate the possible association of PNPLA3-I148M gene variant with the severity of liver fat content and liver fibrosis in Egyptian children with CHC.

Patients and Methods: Fifty normal-weighted children (mean age 10.62±2.59 years) with CHC were subjected to genotyping of PNPLA3-I148M gene variant using the real time PCR TaqMan assay. FibroScan examination for assessment of both liver fibrosis by Fibroscan liver stiffness (LMS) and liver steatosis by the controlled attenuation parameter (CAP) scores and histological examination of liver biopsies for assessment of liver steatosis, and METAVIER scoring for necroinflammatory activity grades and liver fibrosis stages were done for all patients as well as appropriate laboratory investigations. APRI and FIB-4 indices as well as insulin resistance using HOMA-IR were also calculated.

Results: 34 cases (68%) had CC genotype (wild CC genotype) ,9 cases (18%) had CG genotype (heterozygous for the risk G allele) and 7 cases (14%) had GG genotype (homozygous for the risk G allele). Significant higher values of LSM and CAP steatosis scores were found in patients with CG and GG genotypes compared to those with CC genotype. CG gene variant and GG gene variant were significant positive predictive factors for histopathological liver steatosis and fibrosis stages and inflammatory activity grades among the studied patients. Significant higher values of many laboratory variables (AST, fasting blood glucose, fasting serum insulin, and HOMA-IR) but lower platelets count was found in patients with G allele (CG+ GG) compared to patients without G allele (CC). In addition, significant positive correlations between PNPLA3-I148M gene variant and indicators of hepatic steatosis and fibrosis and many laboratory parameters (AST, APRI, FIB4, FBS, fasting serum insulin, and HOMA-IR) but a significant negative correlation between PNPLA3-I148M gene variant and platelet cell count were found among the studied patients.

Conclusion: Data of this study suggested that polymorphisms in the PNPLA3 I148M gene variant could contribute to the severity of hepatic steatosis and fibrosis of the studied Egyptian children with CHC.