RESUMEN
Major histocompatibility complex class I-related chain A (MICA) is a highly polymorphic gene that modulates immune surveillance by binding to its receptor on natural killer cells, and its genetic polymorphisms have been associated with chronic immune-mediated diseases. The progressive form of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), is characterized by accumulation of fat and inflammatory cells in the hepatic parenchyma, potentially leading to liver cell injury and fibrosis. To date, there are no data describing the potential role of MICA in the pathogenesis of NAFLD. Therefore, our aim was to assess the association between MICA polymorphism and NASH and its histologic features. A total of 134 subjects were included. DNA from patients with biopsy-proven NAFLD were genotyped using polymerase chain reaction-sequence-specific oligonucleotide for MICA alleles. Liver biopsies were assessed for histologic diagnosis of NASH and specific pathologic features, including stage of fibrosis and grade of inflammation. Multivariate analysis was performed to draw associations between MICA alleles and the different variables; P ≤ 0.05 was considered significant. Univariate analysis showed that MICA*011 (odds ratio [OR], 7.14; 95% confidence interval [CI], 1.24-41.0; P = 0.04) was associated with a higher risk for histologic NASH. Multivariate analysis showed that MICA*002 was independently associated with a lower risk for focal hepatocyte necrosis (OR, 0.24; 95% CI, 0.08-0.74; P = 0.013) and advanced fibrosis (OR, 0.11; 95% CI, 0.02-0.70; P = 0.019). MICA*017 was independently associated with a higher risk for lymphocyte-mediated inflammation (OR, 5.12; 95% CI, 1.12-23.5; P = 0.035). Conclusion: MICA alleles may be associated with NASH and its histologic features of inflammation and fibrosis. Additional research is required to investigate the potential role of MICA in increased risk or protection against NAFLD.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Adulto , Alelos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/patología , Polimorfismo GenéticoRESUMEN
The human leukocyte antigen (HLA) genes may play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH). The aim of this study was to assess the association of HLA class I and II alleles with NASH and its histological features.Deoxyribonucleic acid (DNA) was extracted from 140 subjects (85 biopsy-proven NAFLD and 55 controls) and genotyped for HLA (-A, -B, -C, -DR1, -DR3, -DQ, and -DP). Liver biopsies were assessed for presence of NASH, degree of fibrosis and inflammation. Multivariate analysis was performed to assess associations between HLA genes and different histologic features of NAFLD.Our data for HLA class I showed that HLA-C*4 was associated with lower risk for histologic NASH and HLA-C*6 was protective against portal fibrosis. Conversely, HLA-B*27 was associated with high-grade hepatic steatosis, while HLA-A*31 was associated with increased risk for advanced fibrosis. Among HLA class II alleles, HLA-DQA1*01 was associated with lower risk for NASH while HLA-DRB1*03 was associated with increased risk for NASH.Our findings indicate that HLA class I and II gene polymorphism may be associated with susceptibility to NASH, fibrosis and other pathologic features and may be involved in the pathogenesis of NAFLD.