The Association Of Tlr4 And Cd14 Gene Polymorphisms With Kawasaki Disease Susceptibility And The Development Of Coronary Artery Lesions

Objective: Genetic factors are important in the susceptibility and outcome of KD, to explore the possible association between TLR4 and lipopolysaccharide receptor CD14 gene polymorphisms and Kawasaki disease susceptibility and the development of coronary artery lesions in Kawasaki disease (KD). Determine predictive factors about high risk for coronary artery lesions.Method: This study consisted of KD patients group and normal children as control group, two-color fluorescent staining flow-cytometry was used to detect the expression of TLR4 in peripheral blood white blood cell of 76 Kawasaki disease children and 118 healthy control group. The gene of TLR4 (-896A/G), (-1196C/T) and CD14 (-260C/T) polymorphisms was identified by Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and we analyze the relationship between genotype and Kawasaki disease. The serum TNF-αof two groups was detected by Enzyme-Linked Immunosorbnent Assay (ELISA).Result:(1) The values of mean fluorescence intensity (MFI) of TLR4 in peripheral blood white blood cell of the Kawasaki disease groups and the healthy control groups were 2.87±0.96, 10.55±4.87, 23.36±8.28 and 3.26±0.65, 7.55±1.21, 25.41±6.97, respectively; TLR4 expressed on mononuclear cell mainly, while on lymphocyte,neutrophilic leukocyte, little was detected ; However, no statistically difference was found among the KD and the control.(2) We did not find (-896A/G), (-1196C/T) polymorphisms of TLR4 gene in both groups.(3) The frequency of each genotype of CD14 gene (-260C/T) was 35.5%CC, 30.3%CT, 34.2%TT in Kawasaki disease and 38.1%CC, 47.5%CT, 14.4%TT in healthy control group(X~2=11.62, P<0.05). The frequency of each genotype was significantly different in two groups. The genotype frequency of C and T alleles were 50.7%, 49.3% and 61.9%, 38.1% in Kawasaki disease group and healthy control group. The difference between the two group had a statistical significance(X2=4.76, P<0.05). The relative risk for Kawasaki disease in T allele carriers was 1.58 times as high as that in C allele carriers.(4) The serum levels of TNF-αin KD patients (73.9±21.7ng/ml) were significantly higher than those in the healthy group (19.36±8.25ng/ml) (t=2.047, p<0.05).(5) The distributions of allele were of statistically significant difference between two groups, too; However, no statistically significant difference was found among the KD coronary artery lesions and non-coronary artery lesions(X~2=0.921, P>0.05). The relative risk for KD+CAL in T allele carriers was 1.256 times as high as that in C allele carriers. Conclusion: The gene of TLR4 (-896A/G), (-1196C/T) polymorphisms are not associated with Kawasaki disease. CD14 gene (-260C/T) T allele is associated with Kawasaki disease, and it might be a genetic predisposing predictor for Kawasaki disease.