Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients.

Abstract

BACKGROUND:

To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes.

METHODS:

We selected four (rs683369, rs2282143, rs622342 and rs1443844) OCT-1 single nucleotide polymorphisms (SNPs), and genotyped these SNPs using the TaqMan probe method in 275 Japanese PBC patients and 194 gender-matched, healthy volunteers as controls.

RESULTS:

The Chi-square test revealed that the rs683369 variant allele (G) was associated with insusceptibility to PBC development [P = 0.009, odds ratio (OR) 0.60, 95 % confidence interval (CI) 0.40-0.88] in an allele model, and that the rs683369 variant allele (G) was associated with jaundice-type progression in a minor allele dominant genotype model (P = 0.032, OR 3.10, 95 % CI 1.05-9.14). The OCT-1 rs2282143 variant (T) and rs622342 variant (C) were also associated with jaundice-type progression in a minor allele recessive genotype model (P = 0.0002, OR 10.58, 95 % CI 2.36-47.54, and P = 0.006, OR 7.84, 95 % CI 1.39-44.36, respectively). Furthermore, the association of OCT-1 rs683369 and rs622342 with susceptibility to jaundice-type progression was confirmed by a replication study with a distinct set of PBC patients who underwent liver transplantation.

CONCLUSIONS:

The present study is the first report on the association of OCT-1 genetic polymorphisms with the overall development and jaundice-type progression of PBC.

• Authors: Yuki Ohishi, Makoto Nakamuta, Naoko Ishikawa, Ohki Saitoh, Hitomi Nakamura, Yoshihiro Aiba, Atsumasa Komori, Kiyoshi Migita, Hiroshi Yatsuhashi, Nobuyoshi Fukushima, Motoyuki Kohjima, Tsuyoshi Yoshimoto, Kunitaka Fukuizumi, Makoto Ishibashi, Takashi Nishino, Ken Shirabe, Akinobu Taketomi, Yoshihiko Maehara, Hiromi Ishibashi, Minoru Nakamura, PBC Study Group of NHOSLJ
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 49 Issue 2 Pg. 332-42 (Feb 2014) ISSN: 1435-5922 [Electronic] Japan
• PMID: 23612856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Organic Cation Transporter 1

Topics

• Adult
• Aged
• Case-Control Studies
• Disease Progression
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Humans
• Japan
• Jaundice (etiology, genetics)
• Liver Cirrhosis, Biliary (complications, genetics, pathology)
• Male
• Middle Aged
• Organic Cation Transporter 1 (genetics)
• Polymorphism, Single Nucleotide