Zafra German, Flórez Oscar, Morillo Carlos A, Echeverría Luis Eduardo, Martín Javier, González Clara Isabel
Grupo de Inmunología y Epidemiología Molecular, Escuela de Bacteriología, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Mem Inst Oswaldo Cruz. 2008 Feb;103(1):27-30. doi: 10.1590/s0074-02762008000100004.
The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2) and TLR4 gene polymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln) polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6% and 1.8% respectively). The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.
本研究的目的是检测Toll样受体2(TLR2)和TLR4基因多态性在确定恰加斯病易感性方面的可能影响。通过聚合酶链反应-限制性片段长度多态性对来自哥伦比亚的475名个体进行基因分型,其中143名血清学阳性且患有恰加斯性心肌病,132名血清学阳性且无症状,200名血清学阴性。在所分析的组中未发现TLR2第753位残基精氨酸到谷氨酰胺的替换(Arg753Gln)多态性。TLR4 Asp299Gly和Thr399Ile多态性处于连锁不平衡状态,并且我们在研究人群中观察到这些多态性的频率非常低(分别为2.6%和1.8%)。血清学阴性和血清学阳性个体中TLR2和TLR4的等位基因及基因型总体分布无显著差异。我们比较了无症状患者与患有恰加斯性心肌病患者之间的频率,未观察到等位基因或基因型分布有任何显著差异。总之,本研究证实了在其他人群中观察到的TLR2和TLR4多态性的低频率,并表明这些多态性在恰加斯病中不发挥重要作用。需要在独立队列中验证这些发现,以牢固确立TLR2和TLR4变体在恰加斯病中的作用。