The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response

Abstract

Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254–3.393; P = 0.004) was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411–0.928; P = 0.020) provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (P = 0.021). Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings.

Preserved Gut Microbial Diversity Accompanies Upregulation of TGR5 and Hepatobiliary Transporters in Bile Acid–Treated Animals Receiving Parenteral Nutrition

“…Data suggest that a hepatoprotective effect upon bile acid treatment in PN‐infused animals is contributed via gut FXR activation leading to FGF19 secretion, thus influencing the FXR‐FGF19 axis 6 . Recent data from cell culture and animal studies show that bile acids can also directly influence cholestasis via the key hepatic bile acid transporter BSEP 18 , 42 . ‐ 45 …”

Recent advances in the exploration of the bile salt export pump (BSEP/ABCB11) function

“…The frequent V444A variant and numerous rare mutations have been identified as risk factors for cholestatic DILI [52,60,61]. In addition to ICP and DILI, numerous BSEP variants are associated with several other liver diseases including primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), primary intrahepatic stones, gallstone disease, and neonatal cholestasis [70][71][72]. Despite the substantial amount of genomic data accumulated in the last decade, the etiological role of these BSEP mutations and SNPs in the acquired cholestatic liver diseases remains to be established.…”

Looking Into the Crystal Ball: Predicting Non-response to Ursodeoxycholic Acid in Primary Biliary Cholangitis

“…For example, in a recent study using pre-biopsy serum samples of 136 PBC individuals, pre-treatment serum concentrations of IL-8 and soluble CD14 were associated with poor outcome (Umemura et al, 2016). In a Chinese population, the common single nucleotide variant rs2287618 (p.A444V) in the bile salt export pump ( ABCB11 ) gene was significantly underrepresented in UDCA responsive PBC (Chen et al, 2014). In the UK-PBC cohort including 2353 patients, male gender and younger age were correlated to UDCA failure (Carbone et al, 2013).…”