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海得拉巴市合并糖尿病的肺结核患者及其家庭接触者的白细胞介素-6和白细胞介素-18细胞因子基因变异

IL-6 and IL-18 cytokine gene variants of pulmonary tuberculosis patients with co-morbid diabetes mellitus and their household contacts in Hyderabad.

作者信息

Ponnana Meenakshi, Sivangala Ramya, Joshi Lavanya, Valluri Vijayalakshmi, Gaddam Sumanlatha

机构信息

Department of Immunology, Bhagwan Mahavir Medical Research Center, Hyderabad, India.

Department of Immunology, Bhagwan Mahavir Medical Research Center, Hyderabad, India; Department of Genetics, Osmania University, Hyderabad, India.

出版信息

Gene. 2017 Sep 5;627:298-306. doi: 10.1016/j.gene.2017.06.046. Epub 2017 Jun 23.

Abstract

PURPOSE

Association of cytokine genes reflects their susceptibility towards infection and disease in household contacts (HHC) of pulmonary tuberculosis (PTB) patients. Hyperglycemia, a common factor in diabetics might influence their risk towards mycobacterium tuberculosis infection and disease development. This study determines the association of IL-6 and IL-18 cytokine gene variants of TB patients with diabetes mellitus (TBDM) and their HHC in Hyderabad.

METHODS

Single nucleotide polymorphisms of IL-6 (-174 G>C and -572 G>C) and IL-18 (-137 G>C and -607 C>A) cytokine genes were genotyped by Amplification Refractory Mutation System and Restriction Fragment Length polymerase chain reaction in total of 705 subjects comprising of TBDM, their HHC, PTB, DM and Healthy controls (HC).

RESULTS

At IL-6 -174G>C variant, GG genotype, G allele in TBDM and TBDM HHC, at -572G>C variant, C allele in TBDM and GG haplotype in TBDM HHC were showing positive association, however DM have not shown any association at IL-6 polymorphic sites. With respect to the IL-18 gene polymorphisms, at -137 G>C variant, GG genotype was positively associated in PTB while at -607 C>A variant positive association was shown with AC genotype in TBDM, their HHC and DM; GACC diplotype in TBDM and GCGC in PTB.

CONCLUSION

Our findings suggest that susceptible combination of IL-6 and IL-18 cytokine genes associated with disease in the HHCs highlight their risk of inclination towards the disease.

摘要

目的

细胞因子基因的关联反映了肺结核(PTB)患者家庭接触者(HHC)对感染和疾病的易感性。高血糖是糖尿病患者的常见因素,可能会影响他们感染结核分枝杆菌和疾病发展的风险。本研究确定了海得拉巴糖尿病合并肺结核(TBDM)患者及其HHC中白细胞介素-6(IL-6)和白细胞介素-18(IL-18)细胞因子基因变异的关联。

方法

采用扩增阻滞突变系统和限制性片段长度聚合酶链反应对705名受试者(包括TBDM患者、其HHC、PTB患者、糖尿病患者和健康对照者(HC))的IL-6(-174 G>C和-572 G>C)和IL-18(-137 G>C和-607 C>A)细胞因子基因的单核苷酸多态性进行基因分型。

结果

在IL-6 -174G>C变异位点,TBDM患者及其HHC中的GG基因型、G等位基因,在-572G>C变异位点,TBDM患者中的C等位基因以及TBDM患者HHC中的GG单倍型显示出正相关,然而糖尿病患者在IL-6多态性位点未显示出任何关联。关于IL-18基因多态性,在-137 G>C变异位点,PTB患者中的GG基因型呈正相关,而在-607 C>A变异位点,TBDM患者及其HHC以及糖尿病患者中的AC基因型呈正相关;TBDM患者中的GACC双倍型和PTB患者中的GCGC双倍型。

结论

我们的研究结果表明,HHC中与疾病相关的IL-6和IL-18细胞因子基因的易感组合突出了他们患该疾病的倾向风险。

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