PMID- 11709756
OWN - NLM
STAT- MEDLINE
DCOM- 20020125
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 70
IP  - 1
DP  - 2002 Jan
TI  - Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with 
      asthma.
PG  - 230-6
AB  - Asthma is a common respiratory disease that is characterized by variable airways 
      obstruction caused by acute and chronic bronchial inflammation; associated 
      phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum 
      immunoglobulin E (IgE) levels, and skin tests positive to common allergens. 
      Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor 
      (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 
      and IL4 are produced by Th2 cells and are capable of inducing isotype 
      class-switching of B-cells to produce IgE after allergen exposure. These 
      cytokines also share a common receptor component, IL4R alpha. We have 
      investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch 
      families ascertained through a proband with asthma. By considering the probands 
      and their spouses as an unrelated sample, we observed significant associations of 
      atopy and asthma-related phenotypes with several IL4RA polymorphisms, including 
      S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction 
      between S478P in IL4RA and the -1111 promoter variation in IL13, previously shown 
      to be associated with BHR (P=.003), was detected. Individuals with the risk 
      genotype for both genes were at almost five times greater risk for the 
      development of asthma compared to individuals with both non-risk genotypes 
      (P=.0004). These data suggest that variations in IL4RA contribute to elevated 
      total serum IgE levels, and interaction between IL4RA and IL13 markedly increases 
      an individual's susceptibility to asthma.
FAU - Howard, Timothy D
AU  - Howard TD
AD  - Center for Human Genomics, Wake Forest University School of Medicine, 
      Winston-Salem, NC 27157, USA.
FAU - Koppelman, Gerard H
AU  - Koppelman GH
FAU - Xu, Jianfeng
AU  - Xu J
FAU - Zheng, Siqun L
AU  - Zheng SL
FAU - Postma, Dirkje S
AU  - Postma DS
FAU - Meyers, Deborah A
AU  - Meyers DA
FAU - Bleecker, Eugene R
AU  - Bleecker ER
LA  - eng
GR  - R01 HL048341/HL/NHLBI NIH HHS/United States
GR  - R01 HL066393/HL/NHLBI NIH HHS/United States
GR  - R01HL/48341/HL/NHLBI NIH HHS/United States
GR  - R01HL/66393/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20011114
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Interleukin-13)
RN  - 0 (Receptors, Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Asthma/*genetics/immunology
MH  - *Epistasis, Genetic
MH  - Exons/genetics
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Interleukin-13/*genetics
MH  - Male
MH  - Middle Aged
MH  - Netherlands
MH  - Odds Ratio
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Interleukin-4/*genetics
MH  - Regression Analysis
PMC - PMC384891
EDAT- 2001/12/13 10:00
MHDA- 2002/01/26 10:01
PMCR- 2002/07/01
CRDT- 2001/12/13 10:00
PHST- 2001/08/28 00:00 [received]
PHST- 2001/10/22 00:00 [accepted]
PHST- 2001/12/13 10:00 [pubmed]
PHST- 2002/01/26 10:01 [medline]
PHST- 2001/12/13 10:00 [entrez]
PHST- 2002/07/01 00:00 [pmc-release]
AID - S0002-9297(07)61296-8 [pii]
AID - 013287 [pii]
AID - 10.1086/338242 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2002 Jan;70(1):230-6. doi: 10.1086/338242. Epub 2001 Nov 14.