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CCL5 在部落人群肺结核感染中的基因型-表型关系:一项初步研究。

Genotype-phenotype relationship of CCL5 in pulmonary tuberculosis infection in tribe: A pilot study.

机构信息

Department of Molecular & Human Genetics, Centre for Genomics, Jiwaji University, Gwalior, India.

Revised National Tuberculosis Control Programme Unit, District Hospital, Sheopur, India.

出版信息

Indian J Med Res. 2017 Dec;146(6):768-773. doi: 10.4103/ijmr.IJMR_1582_15.

DOI:10.4103/ijmr.IJMR_1582_15
PMID:29664036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5926349/
Abstract

BACKGROUND & OBJECTIVES: Sahariya, a primitive tribe of Central India, has shown significantly increased incidence of pulmonary tuberculosis (PTB). Our previous study on Sahariya showed a significant association of -403G>A single nucleotide polymorphism (SNP) of CCL5 with susceptibility to PTB. Hence, this study was aimed to analyze a genotype-phenotype relationship of this disease-associated SNP to develop a potential diagnostic marker for TB in this tribe.

METHODS

The present study was carried out on 70 plasma samples from Sahariya tribe, wherein the plasma CCL5 level was determined using a commercially available ELISA kit.

RESULTS

The level of CCL5 decreased significantly in patients who were on therapy/completed their therapy [inactive TB patient/inactive PTB (IPTB)], particularly with AA genotype of -403G>A (P=0.046). The level, with AA genotype, was also found to gradually decrease in sputum 3+ and 1+/2+ than in sputum-negative samples. Similarly, the CCL5 level was found to be higher in sputum-positive/active TB patients than in IPTB group and healthy controls.

INTERPRETATION & CONCLUSIONS: Our results suggested that the CCL5 level was influenced collectively not only by the genotypes of -403G>A SNP and bacillary load but also by the treatment. Thus, CCL5 may be considered for the development of a diagnostic marker and also as an indicator of recovery.

摘要

背景与目的

印度中部的原始部落撒哈里亚人肺结核(PTB)的发病率显著增加。我们之前对撒哈里亚人的研究表明,CCL5 的-403G>A 单核苷酸多态性(SNP)与 PTB 的易感性显著相关。因此,本研究旨在分析该疾病相关 SNP 的基因型-表型关系,以期为该部落开发潜在的 TB 诊断标志物。

方法

本研究在 70 份来自撒哈里亚部落的血浆样本中进行,其中使用市售 ELISA 试剂盒测定血浆 CCL5 水平。

结果

治疗中/已完成治疗的患者(活动性结核病患者/潜伏性肺结核患者,IPTB)的 CCL5 水平显著降低,尤其是-403G>A 的 AA 基因型(P=0.046)。还发现,与痰阴性样本相比,AA 基因型的 CCL5 水平在 3+和 1+/2+的痰液中逐渐降低。同样,与 IPTB 组和健康对照组相比,痰阳性/活动性结核病患者的 CCL5 水平更高。

解释与结论

我们的结果表明,CCL5 水平不仅受-403G>A SNP 基因型和细菌负荷的影响,还受治疗的影响。因此,CCL5 可被考虑用于开发诊断标志物,也可作为恢复的指标。

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本文引用的文献

1
Pulmonary tuberculosis - a health problem amongst Saharia tribe in Madhya Pradesh.肺结核——中央邦萨哈里亚部落面临的一个健康问题。
Indian J Med Res. 2015 May;141(5):630-5. doi: 10.4103/0971-5916.159560.
2
Distribution of HLA-A, B and DRB1 alleles in Sahariya tribe of North Central India: an association with pulmonary tuberculosis.印度中北部撒哈拉亚部落的 HLA-A、B 和 DRB1 等位基因分布:与肺结核的关联。
Infect Genet Evol. 2014 Mar;22:175-82. doi: 10.1016/j.meegid.2013.08.019. Epub 2013 Aug 28.
3
Genetic polymorphisms of CCL2, CCL5, CCR2 and CCR5 genes in Sahariya tribe of North Central India: an association study with pulmonary tuberculosis.印度中北部的萨哈里亚部落的 CCL2、CCL5、CCR2 和 CCR5 基因的遗传多态性:与肺结核的关联研究。
Infect Genet Evol. 2012 Jul;12(5):1120-7. doi: 10.1016/j.meegid.2012.03.018. Epub 2012 Mar 28.
4
Prevalence of smear-positive pulmonary tuberculosis in different ethnic groups in India: evaluation of public health.印度不同民族中涂片阳性肺结核的流行情况:公共卫生评估。
Public Health. 2012 Apr;126(4):295-9. doi: 10.1016/j.puhe.2011.12.016. Epub 2012 Jan 28.
5
CCL5 (RANTES) gene polymorphisms in pulmonary tuberculosis patients of south India.印度南部肺结核患者 CCL5(RANTES)基因多态性。
Int J Immunogenet. 2011 Oct;38(5):397-402. doi: 10.1111/j.1744-313X.2011.01021.x. Epub 2011 Jun 27.
6
Coding and non-coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India.维生素 D 受体基因中的编码和非编码多态性与印度中部部落、种姓和穆斯林人群的肺结核易感性。
Infect Genet Evol. 2011 Aug;11(6):1456-61. doi: 10.1016/j.meegid.2011.05.019. Epub 2011 May 27.
7
Polymorphisms in the RANTES gene increase susceptibility to active tuberculosis in Tunisia.RANTES 基因多态性增加突尼斯活动性结核病的易感性。
DNA Cell Biol. 2011 Oct;30(10):789-800. doi: 10.1089/dna.2010.1200. Epub 2011 Apr 21.
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Increased prevalence of pulmonary tuberculosis in male adults of sahariya tribe of India: a revised survey.印度萨哈里亚部落成年男性肺结核患病率上升:一项修订调查
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CCL5 participates in early protection against Mycobacterium tuberculosis.CCL5 参与早期抗结核分枝杆菌保护。
J Leukoc Biol. 2010 Jun;87(6):1153-65. doi: 10.1189/jlb.1109742. Epub 2010 Apr 6.
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