Genetic variant in the abo locus enhances liver stiffness among patients with non-viral hepatitis

Abstract

Background: Liver fibrosis is a common hallmark of ongoing liver injury. Although several candidate gene studies have been reported, the genetic background of liver fibrogenesis is still poorly defined. Previously it has been shown that blood groups are associated with the severity of liver injury among patients with chronic hepatitis C virus (HCV) infection [1]. Nevertheless, similar studies in patients with non-viral hepatitis are lacking. Herein we investigate a genetic polymorphism in the ABO locus, a previously identified risk factor for pancreatic cancer that is in a complete linkage disequilibrium with the blood group 0 [2], for its association with the degree of liver fibrosis in a cohort of patients with non-viral hepatitis. Methods: We recruited 289 individuals (age 17 - 80 years, 150 males) with chronic non-viral liver diseases who were phenotyped for hepatic fibrosis non-invasively by transient elastography (TE, Fibroscan). The ABO rs505922 polymorphism was genotyped using a PCR-based assay with 5'-nuclease and fluorescence detection. Results: In total, the [TT], [CT] and [CC] and genotypes were carried by 123 (43%), 133 (46%) and 33 (11%) individuals, respectively, which is in line with the Entrez SNP database ranges. The percentage of [TT] individuals, known to carry blood group 0 [2], was consistent with the blood group 0 distribution in the German population. Of note, homozygous carriers of the [T] allele demonstrated significantly (P = 0.016) higher mean liver stiffness values (18.8 kPa, 95% CI 14.8 - 22.9) as compared to patients with genotypes [CT] and [CC] (n = 166) (13.2 kPa, 95% CI 10.8 - 15.7). On the other hand, comparison of the genotype distribution among patients with mild fibrosis (i.e, TE < 7.5 kPa, n = 110) and severe fibrosis (i.e, TE > 14.5 kPa, n = 156) did not provide evidence for an association with fibrosis (P > 0.05). Conclusions: The common polymorphism at the ABO locus confers an increased risk of liver fibrosis in patients with chronic non-viral liver diseases. In particular, patients with blood group 0 display higher liver fibrosis values as quantified by elastography. Our findings support a potential role of patients' blood groups in fibrosis progression. This phenomenon may be related to enhanced profibrogenic properties of distinctive blood groups and is in line with a previous genome-wide scan identifying an association between the ABO locus and increased plasma liver enzymes levels in the general population [3].