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.
| Original language | English |
|---|---|
| Pages (from-to) | 332-342 |
| Number of pages | 11 |
| Journal | Journal of gastroenterology |
| Volume | 49 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2014 |
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All Science Journal Classification (ASJC) codes
- Gastroenterology
Cite this
Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients. / 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.
In: Journal of gastroenterology, Vol. 49, No. 2, 01.02.2014, p. 332-342.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients
AU - Ohishi, Yuki
AU - Nakamuta, Makoto
AU - Ishikawa, Naoko
AU - Saitoh, Ohki
AU - Nakamura, Hitomi
AU - Aiba, Yoshihiro
AU - Komori, Atsumasa
AU - Migita, Kiyoshi
AU - Yatsuhashi, Hiroshi
AU - Fukushima, Nobuyoshi
AU - Kohjima, Motoyuki
AU - Yoshimoto, Tsuyoshi
AU - Fukuizumi, Kunitaka
AU - Ishibashi, Makoto
AU - Nishino, Takashi
AU - Shirabe, Ken
AU - Taketomi, Akinobu
AU - Maehara, Yoshihiko
AU - Ishibashi, Hiromi
AU - Nakamura, Minoru
PY - 2014/2/1
Y1 - 2014/2/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00535-013-0795-0
DO - 10.1007/s00535-013-0795-0
M3 - Article
VL - 49
SP - 332
EP - 342
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 2
ER -