SNP analysis of genes implicated in T cell proliferation in primary biliary cirrhosis

Sabine Oertelt, Thomas P. Kenny, Carlo Selmi, Pietro Invernizzi, Mauro Podda, M. Eric Gershwin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T lymphocytes as potential effectors of tissue injury. We hypothesized that single nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation would be responsible for uncontrolled expansion of T cells and autoreactivity. To address this, we genotyped DNA from 154 patients with PBC and 166 ethnically matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay. We report herein a statistically significant decrease in homozygosity rate for the 60A*CTLA-4 allele in patients with PBC compared to controls (p = 0.0411). Moreover, we found a significant association of the same allele and of the LYP*T allele with anti-mitochondrial antibody (AMA) serum negativity (p = 0.0304 and 0.0094, respectively). No association between any of the other studied SNPs and PBC susceptibility, progression, or AMA status was observed. In conclusion, given the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases, we encourage a more detailed genetic analysis of this candidate gene. Further, although obtained from a limited number of AMA-negative subjects, our data suggest a potential genetic heterogeneity for this specific subgroup of patients with PBC.

Original languageEnglish (US)
Pages (from-to)259-263
Number of pages5
JournalClinical and Developmental Immunology
Volume12
Issue number4
DOIs
StatePublished - Dec 2005

Fingerprint

Biliary Liver Cirrhosis
Single Nucleotide Polymorphism
Cell Proliferation
T-Lymphocytes
Anti-Idiotypic Antibodies
Genes
Alleles
Genetic Heterogeneity
Genetic Association Studies
Autoimmune Diseases
Lymphocytes
DNA
Wounds and Injuries
Serum

Keywords

  • CTLA-4
  • Foxp3
  • ICOS
  • LYP
  • Primary biliary cirrhosis (PBC)
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Developmental Biology

Cite this

SNP analysis of genes implicated in T cell proliferation in primary biliary cirrhosis. / Oertelt, Sabine; Kenny, Thomas P.; Selmi, Carlo; Invernizzi, Pietro; Podda, Mauro; Gershwin, M. Eric.

In: Clinical and Developmental Immunology, Vol. 12, No. 4, 12.2005, p. 259-263.

Research output: Contribution to journalArticle

Oertelt, Sabine ; Kenny, Thomas P. ; Selmi, Carlo ; Invernizzi, Pietro ; Podda, Mauro ; Gershwin, M. Eric. / SNP analysis of genes implicated in T cell proliferation in primary biliary cirrhosis. In: Clinical and Developmental Immunology. 2005 ; Vol. 12, No. 4. pp. 259-263.
@article{03eac712d70c42bf91eb00cff4ffcfa1,
title = "SNP analysis of genes implicated in T cell proliferation in primary biliary cirrhosis",
abstract = "Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T lymphocytes as potential effectors of tissue injury. We hypothesized that single nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation would be responsible for uncontrolled expansion of T cells and autoreactivity. To address this, we genotyped DNA from 154 patients with PBC and 166 ethnically matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay. We report herein a statistically significant decrease in homozygosity rate for the 60A*CTLA-4 allele in patients with PBC compared to controls (p = 0.0411). Moreover, we found a significant association of the same allele and of the LYP*T allele with anti-mitochondrial antibody (AMA) serum negativity (p = 0.0304 and 0.0094, respectively). No association between any of the other studied SNPs and PBC susceptibility, progression, or AMA status was observed. In conclusion, given the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases, we encourage a more detailed genetic analysis of this candidate gene. Further, although obtained from a limited number of AMA-negative subjects, our data suggest a potential genetic heterogeneity for this specific subgroup of patients with PBC.",
keywords = "CTLA-4, Foxp3, ICOS, LYP, Primary biliary cirrhosis (PBC), Single nucleotide polymorphism (SNP)",
author = "Sabine Oertelt and Kenny, {Thomas P.} and Carlo Selmi and Pietro Invernizzi and Mauro Podda and Gershwin, {M. Eric}",
year = "2005",
month = "12",
doi = "10.1080/17402520500317859",
language = "English (US)",
volume = "12",
pages = "259--263",
journal = "Journal of Immunology Research",
issn = "2314-8861",
publisher = "Hindawi Publishing Corporation",
number = "4",

}

TY - JOUR

T1 - SNP analysis of genes implicated in T cell proliferation in primary biliary cirrhosis

AU - Oertelt, Sabine

AU - Kenny, Thomas P.

AU - Selmi, Carlo

AU - Invernizzi, Pietro

AU - Podda, Mauro

AU - Gershwin, M. Eric

PY - 2005/12

Y1 - 2005/12

N2 - Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T lymphocytes as potential effectors of tissue injury. We hypothesized that single nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation would be responsible for uncontrolled expansion of T cells and autoreactivity. To address this, we genotyped DNA from 154 patients with PBC and 166 ethnically matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay. We report herein a statistically significant decrease in homozygosity rate for the 60A*CTLA-4 allele in patients with PBC compared to controls (p = 0.0411). Moreover, we found a significant association of the same allele and of the LYP*T allele with anti-mitochondrial antibody (AMA) serum negativity (p = 0.0304 and 0.0094, respectively). No association between any of the other studied SNPs and PBC susceptibility, progression, or AMA status was observed. In conclusion, given the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases, we encourage a more detailed genetic analysis of this candidate gene. Further, although obtained from a limited number of AMA-negative subjects, our data suggest a potential genetic heterogeneity for this specific subgroup of patients with PBC.

AB - Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T lymphocytes as potential effectors of tissue injury. We hypothesized that single nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation would be responsible for uncontrolled expansion of T cells and autoreactivity. To address this, we genotyped DNA from 154 patients with PBC and 166 ethnically matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay. We report herein a statistically significant decrease in homozygosity rate for the 60A*CTLA-4 allele in patients with PBC compared to controls (p = 0.0411). Moreover, we found a significant association of the same allele and of the LYP*T allele with anti-mitochondrial antibody (AMA) serum negativity (p = 0.0304 and 0.0094, respectively). No association between any of the other studied SNPs and PBC susceptibility, progression, or AMA status was observed. In conclusion, given the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases, we encourage a more detailed genetic analysis of this candidate gene. Further, although obtained from a limited number of AMA-negative subjects, our data suggest a potential genetic heterogeneity for this specific subgroup of patients with PBC.

KW - CTLA-4

KW - Foxp3

KW - ICOS

KW - LYP

KW - Primary biliary cirrhosis (PBC)

KW - Single nucleotide polymorphism (SNP)

UR - http://www.scopus.com/inward/record.url?scp=30344440791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30344440791&partnerID=8YFLogxK

U2 - 10.1080/17402520500317859

DO - 10.1080/17402520500317859

M3 - Article

C2 - 16584111

AN - SCOPUS:30344440791

VL - 12

SP - 259

EP - 263

JO - Journal of Immunology Research

JF - Journal of Immunology Research

SN - 2314-8861

IS - 4

ER -