A preliminary investigation of the association between haptoglobin polymorphism, serum ferritin concentration and fatty liver disease.

Background: The genetic polymorphism of haptoglobin (HP) has been associated with cardiovascular disease and type 2 diabetes. We hypothesized that the HP polymorphism could affect the incidence of nonalcoholic fatty liver disease (NAFLD).

Methods: This cross sectional case-control analysis included 337 Japanese participants in a health screening program. Fatty liver disease (FLD) was diagnosed by ultrasonography scanning and was classified into NAFLD based on the daily alcohol intake. The HP1 and HP2 alleles were determined using the PCR, and serum ferretin concentrations were measured.

Results: FLD and NAFLD were diagnosed in 91 and 69 subjects, respectively. The adjusted odd ratio (OR) of HP2 carriers vs. non-carriers was 11.8 [95% confidence intervals (CI), 1.3-104.0] for FLD, and 11.7 (95% CI, 1.3-107.9) for NAFLD. Male FLD cases with the HP2/HP2genotype had significantly higher ferretin concentrations than those without (P=0.003). The ferritin concentrations were correlated with the alanine-aminotransferase activities (r=0.48, P<0.001 in FLD cases with the HP2/HP2 genotype). Ferritin was an independent risk factor for FLD, and the incidence of FLD significantly increased in association with ferritin.

Conclusions: This is a preliminary but the first report suggesting the HP2 allele to be a candidate risk factor for NAFLD.