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Toll样受体2(TLR2)基因多态性,即753位精氨酸突变为谷氨酰胺(Arg753Gln)和677位精氨酸突变为色氨酸(Arg677Trp),与印度患者结核病负担增加无关。

TLR2 polymorphisms, Arg753Gln and Arg677Trp, are not associated with increased burden of tuberculosis in Indian patients.

作者信息

Biswas Debasis, Gupta Shailendra K, Sindhwani Girish, Patras Abhishek

机构信息

Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Dehradun 248140, India.

出版信息

BMC Res Notes. 2009 Aug 18;2:162. doi: 10.1186/1756-0500-2-162.

Abstract

BACKGROUND

In view of the role of TLR2 activation in host defense against mycobacteria, the present study was conducted to examine whether TLR2 polymorphisms could account for the increased prevalence of tuberculosis in Indian patients. Detection of such polymorphisms would help in assessing the risk of developing active tuberculosis among contacts or HIV positive patients and in identifying candidates for chemoprophylaxis.

FINDINGS

One hundred patients with tuberculosis and 100 controls were investigated for the presence of two TLR2 polymorphisms, viz. Arg753Gln and Arg677Trp, using PCR-RFLP of a 340 bp region of the TLR2 gene, followed by DNA sequencing of a randomly selected group of 35 patients. While these polymorphisms were found to be non-existent in our study groups, we observed a novel polymorphism Phe749Tyr in 2 patients. However, this polymorphism was associated with negligible deviation in Delphi electrostatic potential and structural alignment from the wild-type TLR2 protein, making it an unlikely candidate for any significant structural or functional alteration at the protein level.

CONCLUSION

Hence we conclude that, contrary to reported associations in other populations, TLR2 polymorphisms are not responsible for the increased prevalence of TB in the Indian population.

摘要

背景

鉴于Toll样受体2(TLR2)激活在宿主抗分枝杆菌防御中的作用,本研究旨在探讨TLR2基因多态性是否可解释印度患者中结核病患病率的增加。检测此类多态性将有助于评估接触者或HIV阳性患者发生活动性结核病的风险,并有助于确定化学预防的候选对象。

研究结果

采用TLR2基因340bp区域的聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP),对100例结核病患者和100例对照者进行了两种TLR2基因多态性即精氨酸753谷氨酰胺(Arg753Gln)和精氨酸677色氨酸(Arg677Trp)的检测,随后对随机选取的35例患者进行DNA测序。虽然在我们的研究组中未发现这些多态性,但我们在2例患者中观察到一种新的多态性苯丙氨酸749酪氨酸(Phe749Tyr)。然而,这种多态性与野生型TLR2蛋白的德尔菲静电势和结构比对的偏差可忽略不计,这使得它不太可能在蛋白质水平上引起任何显著的结构或功能改变。

结论

因此我们得出结论,与其他人群中报道的关联相反,TLR2基因多态性与印度人群中结核病患病率的增加无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31a8/2732632/f2e5765b0b9b/1756-0500-2-162-1.jpg

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