The Association Between Variation Of The Toll Like Receptors Gene And Invasive Aspergillosis In Han Population

Invasive aspergillosis (IA) is not only in immunosuppressed patients,can also be found in the immunocompetent host. TLRs mediate the recognition of fungal and subsequent inflammatory responses through rapid changes in the expression of genes encoding cytokines and inflammatory molecules. Abroad in recent years, there have been many clinical research reports found that polymorphism in TLRs gene was associanted with susceptibility to IA. But all of them was focus on the patients who under a hematopoietic stem cell transplantation. There was no study on the patients without udlying diseases. We found many IA patients without basic diseases on clinical. Because of these hosts do not have any IA susceptible factors, it’s significant to research them. It’s different in gene between Chinese Han population and Caucasian race. No related literatures have been found. Therefore, It’s remains to be research for the gene variant of Han Chines IA patients.Objective To investigate in a clinical setting whether genetic mutations in TLR2and TLR4are associated with susceptibility to invasive aspergillosis.Methods twenty-five patients diagnosed with probable or proven IA were enrolled. Among25patients diagnosed with IA.12patients have base diseases, the others have no underlying disease; The control group consisted of80normal persons and48patients exclude IA. All of the subjects are "Han" population of China. DNA was extracted from peripheral blood. Using the polymerase chain reaction (PCR) to amplified coding sequence of TLR2and TLR4gene. DNA sequence of them were analyzed and the effect on the function of protein was calculated.Results Two TLR2single-nucleotide polymorphisms (SNPs)597T>C,1350T>C have been found, no statistical significance compared with control group. Two missense mutations, TLR4219A>G and1363C＞T, in TLR4were identified in IA patients. Both patients have no underlying diseases.No mutation has been founded in control.219A>G is predicted to impair the ligand-binding domain.Conclusions Variantion in the coding region of TLR4gene may increase the susceptibility to invasive aspergillosis. No particular polymorphism of TLR2was associated with IA.