NOS2A promoter (CCTTT)n association with TB lacks independent functional correlation amongst Indians

Mamata Jena, Amit Kumar Srivastava, Rajnish Kumar Singh, Prithvi Raj Sharma, P. K. Das, Rameshwar N.K. Bamezai

Research output: Contribution to journalArticlepeer-review

Abstract

Summary A penta-nucleotide microsatellite marker (CCTTT)n, in NOS2A promoter region has been associated with a variety of infectious diseases, including Tuberculosis. Most of these studies, however, are limited in justifying the association to tuberculosis through independent functional assays. The present study on 915 individuals from three geographically distinct populations of India focused on the association and function simultaneously. PCR-Polyacrylamide Gel Electrophoresis and direct sequencing revealed the association of (CCTTT)10 allele with protection against Tuberculosis in all the three populations (i) independently: Odisha [p = 0.0025, p c = 0.025, OR (95%CI) = 0.5 (0.39-0.82)], Chhattisgarh-tribe [p = 0.0001, pc = 0.001, OR (95%CI) = 0.3 (0.19-0.60)] and Sahariya tribe [p = 0.02, pc = 0.2, OR (95%CI) = 0.27 (0.08-0.84)]; and (ii) together: [p < 0.0001, pc < 0.001, OR (95%CI) = 0.47 (0.35-0.63)]. In-vitro dual luciferase reporter assay revealed that (CCTTT) n microsatellite affected the expression of the reporter gene without enhancing the promoter strength in repeat-size specific manner. Thus the genetic association observed did not correlate exactly with the expression pattern and probably depended on flanking promoter SNPs (rs2779249 & rs140293907) not in strong LD with the microsatellite, and this effect needs future confirmation.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalTuberculosis
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • LD
  • Microsatellite
  • NOS2A
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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