NOS2A promoter (CCTTT)n association with TB lacks independent functional correlation amongst Indians
| Autor: | Mamata Jena, Pragnya Das, Amit Kumar Srivastava, Rajnish Kumar Singh, Prithvi R. Sharma, Rameshwar N. K. Bamezai |
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| Rok vydání: | 2013 |
| Předmět: |
Microbiology (medical)
Adult Male Genotype Immunology India Nitric Oxide Synthase Type II Single-nucleotide polymorphism Biology Microbiology Polymorphism Single Nucleotide Gene Frequency Humans Tuberculosis Genetic Predisposition to Disease Allele Promoter Regions Genetic Genetic association Gel electrophoresis Genetics Reporter gene Luminescent Agents Functional correlation Promoter Mycobacterium tuberculosis Molecular biology Luciferases Bacterial Infectious Diseases Case-Control Studies Microsatellite Electrophoresis Polyacrylamide Gel Female Microsatellite Repeats |
| Zdroj: | Tuberculosis (Edinburgh, Scotland). 94(1) |
| ISSN: | 1873-281X |
| Popis: | 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, pc = 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 (rs2779249rs140293907) not in strong LD with the microsatellite, and this effect needs future confirmation. |
| Databáze: | OpenAIRE |
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