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

Autor: Ohishi, Yuki, Nakamuta, Makoto, Ishikawa, Naoko, Saitoh, Ohki, Nakamura, Hitomi, Aiba, Yoshihiro, Komori, Atsumasa, Migita, Kiyoshi, Yatsuhashi, Hiroshi, Fukushima, Nobuyoshi, Kohjima, Motoyuki, Yoshimoto, Tsuyoshi, Fukuizumi, Kunitaka, Ishibashi, Makoto, Nishino, Takashi, Shirabe, Ken, Taketomi, Akinobu, Maehara, Yoshihiko, Ishibashi, Hiromi, Nakamura, Minoru
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Zdroj: Journal of Gastroenterology; Feb2014, Vol. 49 Issue 2, p332-342, 11p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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