The lack of association between four point mutations in the promoter region of the toll-like 4 receptor gene and myocardial infarction.
The toll-like receptor 4 gene product (TLR4) has been implicated in the pathogen recognition response mechanism because it plays a central role in the transcriptional activation of the host defense system. Activation of TLR4 initiates an intracellular signaling cascade, via the adapter protein MyD88 (myeloid differentiation factor 88), which leads to the activation of NF-kappaB transcriptional factor, and ultimately to the induction of a pro-inflammatory response. This inflammatory response has been increasingly associated with atherosclerosis. Recent analyses on two polymorphisms of TLR4, which affect the extracellular domain of the receptor, have been shown to give rise to an attenuated innate immune defense which may contribute to disease susceptibility. We have investigated the significance of four new substitutions found by re-sequencing in the 5'-proximal promoter region of the TLR4 gene in a case-control study of acute myocardial infarction. Our results found no statistically significant association between these genetic variants and MI.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Christine
C
De Staercke
Cathy
C
Lally
Harland
H
Austin
Carla
C
Winston
Nicole
N
Dowling
Byron
B
Williams
W Craig
WC
Hooper
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4