The Relationship of Angiotensin I-Converting Enzyme Genotype to Liver Fibrogenesis in Non-Alcoholic Steatohepatitis

Abstract
Background: Multiple genetic and environmental factors may lead to fibrogenesis in patients with Non-alcoholic fatty liver (NAFL). Many studies investigated the relation of angiotensin I-converting enzyme (ACE) genotyping to liver fibrosis in chronic liver disease; and the results are contradic-tory.
Aim of Study: In the current study, ACE genotype was assessed in NAFLD patients to show its possible association with development liver fibrosis.
Subjects and Methods: The study included 162 patients of NAFLD disease, 49 (30.25%) patients with mild fibrosis, 65 (40.12%) with moderate fibrosis and 48 (29.63%) with severe fibrosis in addition to 138 volunteers was enrolled as a healthy controls. All patients and controls were investigated to serum glucose and fasting insulin level and HOMA-IR was calculated. Liver function tests, both serum ACE and trans-forming growth factor-beta (TGF-b) were done. ACE geno-typing [insertion/deletion (I/D)] was done by PCR.
Results: Fasting glucose and insulin, HOMA-IR, AST, ALT and GGT were significantly higher in NAFLD patients than healthy controls. The homozygous frequency I/I and D/D or D/I of ACE were not significantly different between NAFLD patients and controls. The D/D genotype was associated significantly with the severity of liver fibrosis, D/I polymor-phism with moderate fibrosis and I/I genotype with mild fibrosis. The higher D allele frequency was associated with severe fibrosis, while I allele was frequent in mild fibrosis. The HOMA-IR, ALT, serum ACE and TGF-b were increased significantly in the patients carrying D/D homozygous gene more than those carrying homozygous I/I or D/I polymorphism. The serum ACE and TGF-b were significantly higher in NAFLD patients compared to control and the most higher levels was reported in cases with severe liver fibrosis than moderate and mild liver fibrosis.
Conclusion: ACE (D/D) genotype was closely associated with liver fibrosis severity and ACE (I/D) polymorphism was observed in moderate stage of fibrosis. The allele D is seems to be a risk factor for liver fibrosis development than allele I. The knowledge of the ACE genotypes in NAFLD patients may be important for treatment decision in those patients and beneficial in the follow-up of the disease progression.