TY - JOUR
T1 - Host defense genes in asthma and sepsis and the role of the environment
AU - Gao, Li
AU - Tsai, Yuhjung J.
AU - Grigoryev, Dmitry N.
AU - Barnes, Kathleen C.
PY - 2007/12
Y1 - 2007/12
N2 - PURPOSE OF REVIEW: There is growing evidence that innate immunity genes contribute to asthma pathogenesis. At the core of the innate immune response are ubiquitous, soluble fragments of bacterial lipopolysaccharide or endotoxin, and chronic exposure to domestic endotoxin has been shown to influence asthma severity. Asthmatic and atopic individuals are more sensitive to endotoxin than nonallergic individuals, suggesting a role for genetics in the innate immunity response, and the potential for gene-environment interactions. Variants in genes associated with classic innate immunity-related disorders, such as sepsis, may be unique candidates for asthma susceptibility. RECENT FINDINGS: Candidate genes for asthma and allergic diseases co-associated with sepsis including innate immunity receptors and related molecules (CD14, TLR4 and AOAH) and novel genes such as MYLK provide good examples of pleitropic effects of innate immunity genes, where variants conferring risk to specific traits (i.e. sepsis) under one set of genetic and environmental circumstances confer a reduced risk in a different (but possibly related) clinical outcome (i.e. allergic asthma), and support the 'common variant/multiple disease' hypothesis. SUMMARY: Collectively, these observations suggest a greater role for the innate immunity response in allergic asthma than previously assumed, and implicate host defense genes in disease pathology.
AB - PURPOSE OF REVIEW: There is growing evidence that innate immunity genes contribute to asthma pathogenesis. At the core of the innate immune response are ubiquitous, soluble fragments of bacterial lipopolysaccharide or endotoxin, and chronic exposure to domestic endotoxin has been shown to influence asthma severity. Asthmatic and atopic individuals are more sensitive to endotoxin than nonallergic individuals, suggesting a role for genetics in the innate immunity response, and the potential for gene-environment interactions. Variants in genes associated with classic innate immunity-related disorders, such as sepsis, may be unique candidates for asthma susceptibility. RECENT FINDINGS: Candidate genes for asthma and allergic diseases co-associated with sepsis including innate immunity receptors and related molecules (CD14, TLR4 and AOAH) and novel genes such as MYLK provide good examples of pleitropic effects of innate immunity genes, where variants conferring risk to specific traits (i.e. sepsis) under one set of genetic and environmental circumstances confer a reduced risk in a different (but possibly related) clinical outcome (i.e. allergic asthma), and support the 'common variant/multiple disease' hypothesis. SUMMARY: Collectively, these observations suggest a greater role for the innate immunity response in allergic asthma than previously assumed, and implicate host defense genes in disease pathology.
KW - Asthma
KW - Lipopolysaccharide
KW - Polymorphism
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=35948987588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35948987588&partnerID=8YFLogxK
U2 - 10.1097/ACI.0b013e3282f1fb9a
DO - 10.1097/ACI.0b013e3282f1fb9a
M3 - Review article
C2 - 17989521
AN - SCOPUS:35948987588
SN - 1528-4050
VL - 7
SP - 459
EP - 467
JO - Current opinion in allergy and clinical immunology
JF - Current opinion in allergy and clinical immunology
IS - 6
ER -