Variations Of ABCB4and ABCB11Gene Are Associated With Primary Intrahepatic Stone

Objectives: By sequencing a larger sample size of primary intrahepatic stone (PIS)andnormal population analysis，to investigate whether the variations of ABCB4and ABCB11are associated with PIS.Methods: we applied gene exon sequencing to detect all ABCB4and ABCB11exonsin176PIS patients and178healthy subjects.Results: we applied gene exon sequencing to detect all ABCB4and ABCB11exons in176PIS patients and178healthy subjects. In this study, we identified two mutations inABCB4(No.22677and No.69233G>A) to be associated with PIS for the firstplace(P<0.001，P<0.001). A missense mutation at No.22677was detected in exon6ofABCB4in20heterozygous patients with PIS. Another synonymous mutation at No.69233G>A was detected in exon26of ABCB4in23heterozygous patients with PIS. Thismutation was not related to a change in protein expression but to a reduced rate ofrecurrence of PIS (p=0.01). Meanwhile, we identified three mutations (rs118109635，rs497692and rs497616) in ABCB11that were associated with PIS(p=0.04, p=0.02，P=0.01,respectively). The missense mutation rs118109635was detected in exon21of ABCB11andassociated with increased expression of ABCB11protein (p=0.032), with potential effectsin altering BSEP function. Another two synonymous mutations (rs497692å'Œrs497616) wasdetected in exon24and9of ABCB11. The synonymous mutation rs497692was founded todecrease the expression of ABCB11protein (p=0.001). Both mutations(rs118109635å'Œrs497692) were associated with preoperative jaundice (p=0.00, p=0.03, respectively). Thelevel of Glutamyltransferase, Alkaline Phosphatase and Direct Bilirubin were increased bythe mutation of rs118109635(P=0.02, P=0.046,P=0.02, respectively). The mutation ofrs497692significant increased the globulin level (P=0.002).Conclusions: our study provided evidences showing that ABCB4and ABCB11areprobably promising candidate genes for evaluating PIS risk; the mutations may alter the expressions and functions of the proteins and may be associated with the formation of PIS.