PMID- 10498633
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20101118
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 30
IP  - 4
DP  - 1999 Oct
TI  - Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune 
      hepatitis.
PG  - 851-6
AB  - Genetic involvement in type 1 autoimmune hepatitis (AIH) is indicated by a marked 
      female preponderance and strong, well-established, human leukocyte antigen (HLA) 
      associations. These associations, however, are not universal and a number of 
      genes outside the major histocompatibility complex may also play a role in 
      susceptibility to type 1 AIH. Prime candidates at present are those polymorphic 
      genes encoding the proinflammatory and immunoregulatory cytokines. The aim of 
      this study was to investigate, for the first time, 2 members of the interleukin-1 
      (IL-1) family (IL-1B and IL-1RN), 3 polymorphic sites in the interleukin-10 
      (IL-10) gene promoter (positions -1082, -819, and -592), and 2 polymorphisms in 
      the tumor necrosis factor-alpha (TNF-alpha) promoter (positions -308 and -238) in 
      type 1 AIH. The study was performed on 2 independently collected DNA banks, each 
      with appropriate controls, and throughout the analysis associations described in 
      the first set were confirmed in the second set. Standard polymerase chain 
      reaction (PCR)-based genotyping techniques were used. Overall there were no 
      significant differences in the distributions of the IL-1B and IL-10 alleles, 
      genotypes, or haplotypes in either study set. In contrast we report a significant 
      association between type 1 AIH and TNF*2 (first set: 34% of controls vs. 49% of 
      patients, Pc =.014 and second set: 26% vs. 56%, P =.00008). However, TNF*2 is 
      found in strong linkage disequilibrium with the HLA A1-B8-DR3 haplotype and 
      stratification analysis indicates that the association with TNF*2 is 
      interdependent with HLA DRB1*0301. This is an indication that there is more than 
      one susceptibility allele for type 1 AIH on chromosome 6p21.3.
FAU - Cookson, S
AU  - Cookson S
AD  - Institute of Liver Studies, King's College Hospital, London, UK.
FAU - Constantini, P K
AU  - Constantini PK
FAU - Clare, M
AU  - Clare M
FAU - Underhill, J A
AU  - Underhill JA
FAU - Bernal, W
AU  - Bernal W
FAU - Czaja, A J
AU  - Czaja AJ
FAU - Donaldson, P T
AU  - Donaldson PT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Cytokines)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (IL1RN protein, human)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Cytokines/*genetics
MH  - Female
MH  - Genetic Linkage
MH  - Genetic Predisposition to Disease/genetics
MH  - Genotype
MH  - HLA-B8 Antigen/genetics
MH  - Hepatitis, Autoimmune/*genetics
MH  - Humans
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - Interleukin-1/genetics
MH  - Interleukin-10/genetics
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Genetic/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Reference Values
MH  - Sialoglycoproteins/genetics
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - S0270913999004310 [pii]
AID - 10.1002/hep.510300412 [doi]
PST - ppublish
SO  - Hepatology. 1999 Oct;30(4):851-6. doi: 10.1002/hep.510300412.