A polymorphism in the integrin αV subunit gene affects the progression of primary biliary cirrhosis in Japanese patients.
BACKGROUND
Accumulating evidence indicates that multiple genetic factors are involved in the pathogenesis of primary biliary cirrhosis (PBC). The aim of this study was to investigate whether polymorphisms of the integrin αV subunit gene (ITGAV), a component of integrin αVβ6, which plays an important role in the process of fibrosis, are associated with susceptibility to the onset and/or progression of PBC.


METHODS
In the primary study, eight tag single nucleotide polymorphisms (SNPs) in ITGAV were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, direct DNA sequencing, or high-resolution melting curve analysis in 309 Japanese patients with PBC who were registered in the National Hospital Organization Study Group for Liver Disease in Japan (PBC cohort I) and 293 gender-matched healthy Japanese volunteers (control subjects). For the replication study, 35 PBC patients who progressed to end-stage hepatic failure and underwent liver transplantation (PBC cohort II) were also analyzed.


RESULTS
Three tag SNPs (rs3911238, rs10174098, and rs1448427) in ITGAV were significantly associated with the severe progression of PBC, but not with susceptibility to the onset of PBC, in the primary study (PBC cohort I). Among these SNPs, rs1448427 was also significantly associated with the severe progression to end-stage hepatic failure in the replication study of PBC patients who underwent liver transplantation (PBC cohort II).


CONCLUSIONS
ITGAV is a genetic determinant for the severe progression of PBC in Japanese patients. Genetic polymorphisms of ITGAV may be useful for identifying high-risk Japanese PBC patients, including those who will require liver transplantation, at the time of initial diagnosis.
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Tatsuo
T
Inamine
Minoru
M
Nakamura
Ayumi
A
Kawauchi
Yayoi
Y
Shirakawa
Hisae
H
Hashiguchi
Yoshihiro
Y
Aiba
Akinobu
A
Taketomi
Ken
K
Shirabe
Makoto
M
Nakamuta
Shigeki
S
Hayashi
Takeo
T
Saoshiro
Atsumasa
A
Komori
Hiroshi
H
Yatsuhashi
Shinji
S
Kondo
Katsuhisa
K
Omagari
Yoshihiko
Y
Maehara
Hiromi
H
Ishibashi
Kazuhiro
K
Tsukamoto
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D007564:Japan; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D039564:Integrin alphaV