PMID- 16159888
OWN - NLM
STAT- MEDLINE
DCOM- 20060605
LR  - 20091119
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 14
IP  - 21
DP  - 2005 Nov 1
TI  - Association of the IL12RB1 promoter polymorphisms with increased risk of atopic 
      dermatitis and other allergic phenotypes.
PG  - 3149-59
AB  - Atopic dermatitis (AD) is frequently associated with eosinophilia, highly 
      elevated immunoglobulin E (IgE) levels and increased levels of T-helper 2-type 
      (Th2) cytokines in skin lesions due to infiltrating T cells. Interleukin-12 
      (IL-12), in combination with interferon-gamma (IFN-gamma), inhibits IgE synthesis 
      and Th2 cell function. As the IFN-gamma-inducing cytokines IL-12 and IL-23 
      utilize IL-12Rbeta1 as part of their receptors, it is possible that polymorphic 
      variants of the IL-12Rbeta1 (IL12RB1) gene might determine an individual's 
      susceptibility to AD. Here, we carried out a systemic search for genetic variants 
      of the human IL12RB1 in Japanese subjects and identified 48 genetic variants. In 
      a case-control association study, we found that promoter polymorphisms -111A/T 
      and -2C/T were significantly associated with an increased risk of AD under a 
      recessive model. The -111T-allele frequency in the independent population of 
      child asthmatics was also much higher than that in the control group. In 
      addition, the -111T/T genotype was progressively more common in AD with high 
      total serum IgE levels in an IgE-level-dependent manner. Deletion analysis of the 
      IL12RB1 promoter suggested that the -265 to -104 region that contained the 
      -111A/T polymorphic site harbored an important regulatory element. Furthermore, 
      we showed that the -111A/T substitution appeared to cause decreased gene 
      transcriptional activity such that cells from -111A/A individuals exhibited 
      higher IL12RB1 mRNA levels than those from -111T allele carriers. Our results 
      suggested that in individuals with the -111T/T genotype, reduced IL-12Rbeta1 
      expression may lead to increased Th2 cytokine production in the skin and 
      contribute to the development of AD and other subsequent allergic diseases.
FAU - Takahashi, Naomi
AU  - Takahashi N
AD  - Laboratory of Genetics of Allergic Diseases, SNP Research Center, RIKEN, 
      Kanagawa, Japan.
FAU - Akahoshi, Mitsuteru
AU  - Akahoshi M
FAU - Matsuda, Akira
AU  - Matsuda A
FAU - Ebe, Kouji
AU  - Ebe K
FAU - Inomata, Naoko
AU  - Inomata N
FAU - Obara, Kazuhiko
AU  - Obara K
FAU - Hirota, Tomomitsu
AU  - Hirota T
FAU - Nakashima, Kazuko
AU  - Nakashima K
FAU - Shimizu, Makiko
AU  - Shimizu M
FAU - Tamari, Mayumi
AU  - Tamari M
FAU - Doi, Satoru
AU  - Doi S
FAU - Miyatake, Akihiko
AU  - Miyatake A
FAU - Enomoto, Tadao
AU  - Enomoto T
FAU - Nakashima, Hitoshi
AU  - Nakashima H
FAU - Ikezawa, Zenro
AU  - Ikezawa Z
FAU - Shirakawa, Taro
AU  - Shirakawa T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050913
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - 0 (IL12RB1 protein, human)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-12)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cytokines/metabolism
MH  - DNA Primers
MH  - Dermatitis, Atopic/*genetics
MH  - Female
MH  - Gene Components
MH  - Gene Expression Regulation/*genetics
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genetic Testing
MH  - Genotype
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Japan
MH  - Luciferases
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Interleukin/*genetics/metabolism
MH  - Receptors, Interleukin-12
MH  - Sequence Analysis, DNA
MH  - Th2 Cells/metabolism
EDAT- 2005/09/15 09:00
MHDA- 2006/06/06 09:00
CRDT- 2005/09/15 09:00
PHST- 2005/09/15 09:00 [pubmed]
PHST- 2006/06/06 09:00 [medline]
PHST- 2005/09/15 09:00 [entrez]
AID - ddi347 [pii]
AID - 10.1093/hmg/ddi347 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2005 Nov 1;14(21):3149-59. doi: 10.1093/hmg/ddi347. Epub 2005 Sep 
      13.