Role of TLR4 Receptor Polymorphisms in Boutonneuse Fever

Abstract

The genetics of the interaction between host and microbes plays an essential role in the survival of the individual and attainment of longevity. The activation of toll-like receptor (TLR)4 plays a key role in natural and clonotypic immune responses. We evaluated whether TLR4 genotype is a component of genetic background protective versus rickettsiosis and whether this background influences longevity. We genotyped for +896A/G TLR4 polymorphism 78 patients affected by Boutonneuse fever, 78 age-matched controls and 78 advanced age individuals from Sicily. The +869G allele, that attenuates receptor signalling, was significantly overrepresented in patients in comparison with age-matched controls. By analyzing data according to gender, this allele was significantly higher in female patients when compared to advanced age women. Pro-inflammatory responses are programmed to resist fatal infections. So, it is not surprising that the genetic background of people that survive to an advanced age may be protective against infections. However, this seems to occur in women but not in men. In a previous study, the +896G TLR4 allele was overrepresented in advanced age men and underrepresented in men affected by myocardial infarction. Thus, previous and present results tend to agree with the suggestion that men and women may follow different trajectories to reach longevity. For men it might be more important to control atherogenesis, whereas for women it might be more important to control infectious diseases.

New Insight into Immunity and Immunopathology of Rickettsial Diseases

“…Interestingly, it has been demonstrated that the +869G single-nucleotide polymorphism of the TLR4 gene is overexpressed in BF patients with significant differences in the frequency of TLR genotypes and alleles between BF patients and age-matched controls. These data might be interpreted as one hypothetical basis for genetic susceptibility to BF [65]. …”

LPS-mediated production of pro/anti-inflammatory cytokines and eicosanoids in whole blood samples: Biological effects of +896A/G TLR4 polymorphism in a Sicilian population of healthy subjects

“…They have previously been genotyped for the following SNPs: +896A/G TLR4 SNP, À765G/C PTGS2 SNP (rs:20417) and À1708 G/A 5-Lo SNP (no available rs designation) ( Table 1). The procedures for detecting these SNPs have previously been described (Balistreri et al, 2005;Listì et al, 2008). Of 50 individuals, 40 were homozygous for wild-type alleles of +896A/ G TLR4 SNP, and 10 had one or two +896G alleles.…”

A Pilot Study on Prostate Cancer Risk and Pro-Inflammatory Genotypes: Pathophysiology and Therapeutic Implications

“…The DNA samples of the two control groups had been previously extracted from blood samples and genotyped for the six SNPs. The procedure for detecting the +896A/G and +1196C/T TLR4 and +2408 G/A and +2029C/T TLR2 SNPs ( Table 1) was based on Restriction Fragment Length Polymorphism-PCR (RFLP-PCR), restriction cleavage with Nco I, Hinf I, Mwo I and Mps I respectively (New England Biolabs, USA), and separation of DNA fragments by electrophoresis, as previously described [15,16]. The genotyping of -765G/C PTGS2 SNP was performed using RFLP-PCR and with Aci I (New England Biolabs, USA) restriction enzyme, as previously reported [17].…”