HLA-A11 Gene Loci Is Strongly Predictive of Susceptibility to Severe Hepatic Steatosis in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

Abstract

Purpose: The Human Leukocyte Antigen (HLA) is a genetic marker which may be implicated in the pathogenesis of NAFLD. Hepatic steatosis is not only a diagnostic hallmark for NAFLD, but also an independent predictor of cardiovascular diseases. The overall aim of our study is to assess the association between HLA Class I Antigens polymorphism and severe hepatic steatosis. Methods: Blood samples from patients with biopsy-proven NAFLD were genotyped with Polymerase Chain Reaction Sequence Specific Oligonucleotide method (PCR-SSO) for HLA Class I Antigens (HLA-A,-B and-C). Presence and grade of hepatic steatosis was defined histologically. Statistical analysis was performed to draw correlations between HLA Antigen frequencies and the different variables using multivariate analysis, p-values less than 0.05 were considered to be potentially significant. Results: The study cohort include 199 patients with biopsy-proven NAFLD [Age=47.143+/-12.76; Female=137 (69.9%); White=150 (78.5%); Diabetes Mellitus=44 (22.4%); Hyperlipidemia=7 (38.9%)]. Our univariate analyses showed that HLA-A11, -B51, were significantly associated with high grade hepatic steatosis (p=0.02 and 0.04, respectively). Using multivariate analyses, our data demonstrates an independent association between HLA-A11 and high grade hepatic steatosis [Odds Ratio (OR): 0.101 (0.015-0.665) p=0.017]. Additionally, ethnicity also seems to play a role in predisposing to steatosis. There is an association between white race and high grade hepatic steatosis in comparison to the other races (Black, Hispanic and others [OR: 0.021 (0.002-0.238) p=0.001]. We found an interesting strong association between sex and severe steatosis in patients with NAFLD. Females were more at risk of developing severe steatosis than males [OR: 5.387 (1.437-0.20.196), p =0.012]. As expected, BMI plays a major role in susceptibility to high grade hepatic steatosis [OR: 1.312 (1.198-1.436), p =0.000]. Conclusion: HLA-A11 may represent an independent risk factor for development of hepatic steatosis among patients with NAFLD. These HLA risk haplotypes may help identify NAFLD patients with increased risk for developing not only liver disease but also cardiovascular diseases.