Patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism and liver damage in chronic hepatitis C Egyptian patients

• Main Authors: Amal M.H. Mackawy, Mohamed E.H. Badawi, Ola Megahed
• Format: Article
• Language: English
• Published: SpringerOpen 2015-10-01
• Series: Egyptian Journal of Medical Human Genetics
• Subjects: Chronic hepatitis C infection; Steatosis; Liver fibrosis; Genetics; Single nucleotide polymorphism; Patatin-like phospholipase domain-containing protein 3 (PNPLA3)
• Online Access: http://www.sciencedirect.com/science/article/pii/S1110863015000713

Hepatitis C virus (HCV) has been associated with high prevalence of steatosis and fibrosis. The impact of single-nucleotide polymorphisms (SNP) of patatin-like phospholipase domain-containing protein 3 (PNPLA3) on the development of steatosis and fibrosis is not clarified for Egyptian patients with chronic hepatitis C (CHC). The aim of the study was to assess whether the PNPLA3 I148M variant predisposes to steatosis, and to progressive liver damage, as evaluated fibrosis stage in Egyptian patients with CHC. Subjects and methods: 218 CHC Egyptian patients were enrolled in the study, they were grouped by Ishak stage of fibrosis on liver biopsy into group I (fibrosis score 0 or 1; n 81), group II (fibrosis score 2 or 3; n 72) and group III (fibrosis score 4–6; n 65). DNA was amplified by polymerase chain reaction. Results: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI) and lipid levels, but the presence of G allele is associated with higher liver enzymes and viral loads levels. The PNPLA3 G allele was associated with the severity (stage) of fibrosis (X2 = 35.83, P = 0.000). Steatosis was detected in 40.7% of C allele carriers and 58.53% of G allele carriers. The rs738409 G allele was significantly associated with steatosis in the overall CHC patients with different fibrotic stages (X2 = 6.023, P = 0.018) odds ratio (OR) and 95% CI = 1.99 (1.146–3.47). Conclusion: Steatosis and fibrosis severity seems to be PNPLA3 I148M regulated, independently to metabolic parameters but with significant association with viral loads and liver enzymes values in Egyptian patients with CHC.