BACKGROUND: Currently, the primary cause of atherosclerosis remains controversial: while oxidized or enzymatically altered LDL is widely accepted as one cause of the inflamed lesion, microorganisms such as C. pneumoniae or cytomegalovirus (CMV) also have recently been postulated to be involved in the pathogenesis of atherosclerosis. Microbial products activate innate immune cells of the host via Toll-like receptors (TLRs). Common polymorphisms of the TLR-2 and TLR-4 genes have been shown to be associated with an increased risk for restenosis after PTCA, and a lower risk of carotid atherosclerosis, respectively. Microbial DNA has been shown to activate immune cells via the cytosolic TLR-9. Specially, C. pneumonia and CMV as intracellular pathogens may be potent trigger of TLR-9 signaling. Therefore, we investigated whether the two common promotor polymorphisms of the TLR-9 gene are correlated with atherogenesis. METHODS: The T-1237C and the T-1486C polymorphisms were analyzed by Real Time PCR in 202 (derivation study, age 58.1, SD 10.0) and 182 (validation study, age 59.7, SD 9.6) patients that underwent angioplasty and 188 healthy controls (age 52.5, SD 6.1). Restenosis was defined as >50% luminal diameter reduction at follow-up angiography. RESULTS: We found the two polymorphism being able to create new potential binding sites for transcription factors, however, no association of the TLR-9 polymorphisms with atherogenesis or restenosis was detectable. CONCLUSION: Our data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis.
BACKGROUND: Currently, the primary cause of atherosclerosis remains controversial: while oxidized or enzymatically altered LDL is widely accepted as one cause of the inflamed lesion, microorganisms such as C. pneumoniae or cytomegalovirus (CMV) also have recently been postulated to be involved in the pathogenesis of atherosclerosis. Microbial products activate innate immune cells of the host via Toll-like receptors (TLRs). Common polymorphisms of the TLR-2 and TLR-4 genes have been shown to be associated with an increased risk for restenosis after PTCA, and a lower risk of carotid atherosclerosis, respectively. Microbial DNA has been shown to activate immune cells via the cytosolic TLR-9. Specially, C. pneumonia and CMV as intracellular pathogens may be potent trigger of TLR-9 signaling. Therefore, we investigated whether the two common promotor polymorphisms of the TLR-9 gene are correlated with atherogenesis. METHODS: The T-1237C and the T-1486C polymorphisms were analyzed by Real Time PCR in 202 (derivation study, age 58.1, SD 10.0) and 182 (validation study, age 59.7, SD 9.6) patients that underwent angioplasty and 188 healthy controls (age 52.5, SD 6.1). Restenosis was defined as >50% luminal diameter reduction at follow-up angiography. RESULTS: We found the two polymorphism being able to create new potential binding sites for transcription factors, however, no association of the TLR-9 polymorphisms with atherogenesis or restenosis was detectable. CONCLUSION: Our data indicate that the two TLR-9 promotor polymorphisms are not involved in atherogenesis.
Authors: Nadia A Sam-Agudu; Jennifer A Greene; Robert O Opoka; James W Kazura; Michael J Boivin; Peter A Zimmerman; Melissa A Riedesel; Tracy L Bergemann; Lisa A Schimmenti; Chandy C John Journal: Am J Trop Med Hyg Date: 2010-04 Impact factor: 2.345
Authors: A Carvalho; C Cunha; A J Almeida; N S Osório; M Saraiva; M Teixeira-Coelho; S Pedreiro; E Torrado; N Domingues; A G Gomes-Alves; A Marques; J F Lacerda; M G da Silva; M Gomes; A C Pinto; F Torres; P Rendeiro; P Tavares; M Di Ianni; R Medeiros; P Heutink; P M Bracci; L Conde; P Ludovico; J Pedrosa; P Maciel; L Pitzurra; F Aversa; H Marques; A Paiva; C F Skibola; L Romani; A G Castro; F Rodrigues Journal: Genes Immun Date: 2011-08-25 Impact factor: 2.676
Authors: Kamalpreet Nagpal; Theo S Plantinga; Cherilyn M Sirois; Brian G Monks; Eicke Latz; Mihai G Netea; Douglas T Golenbock Journal: J Biol Chem Date: 2011-02-16 Impact factor: 5.157
Authors: N Elloumi; R Fakhfakh; O Abida; L Ayadi; S Marzouk; H Hachicha; M Fourati; Z Bahloul; M N Mhiri; K Kammoun; H Masmoudi Journal: Clin Exp Immunol Date: 2017-08-30 Impact factor: 4.330
Authors: Mike Tsz Hin Ng; Rob Van't Hof; Julie C Crockett; Mairi E Hope; Susan Berry; John Thomson; Mairi H McLean; Kenneth E L McColl; Emad M El-Omar; Georgina L Hold Journal: Infect Immun Date: 2009-12-28 Impact factor: 3.441