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

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

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.

Keywords: CCL5 - resistance - Sahariya - susceptibility - tuberculosis.

MeSH terms

  • Adult
  • Chemokine CCL5 / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Sputum / drug effects
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / microbiology*

Substances

  • CCL5 protein, human
  • Chemokine CCL5