The association between bile salt export pump single-nucleotide polymorphisms and primary biliary cirrhosis susceptibility and ursodeoxycholic acid response.
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).


CONCLUSIONS
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.
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Rui-rui
RR
Chen
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China ; Department of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China.
Yuan-jun
YJ
Li
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Xin-min
XM
Zhou
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Lu
L
Wang
College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
Juan
J
Xing
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Shuang
S
Han
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Li-na
LN
Cui
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Lin-hua
LH
Zheng
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Kai-chun
KC
Wu
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Yong-quan
YQ
Shi
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Zhe-yi
ZY
Han
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Ying
Y
Han
Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an 710032, China.
Dai-ming
DM
Fan
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D014580:Ursodeoxycholic Acid