title: NOS2A promoter (CCTTT)n association with TB lacks independent functional correlation amongst Indians.
abstract: 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 (rs2779249 & rs140293907) not in strong LD with the microsatellite, and this effect needs future confirmation.
authors.affiliation: National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India; Department of Anthropology (C.A.S), Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India. Electronic address: mamata.302@rediffmail.com.
authors.forename: Mamata
authors.initials: M
authors.lastname: Jena
authors.affiliation: National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: amitsrivastava1983@hotmail.com.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.affiliation: National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: rajnishsbt2005@gmail.com.
authors.forename: Rajnish Kumar
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Centre for Genomics, Jiwaji University, Gwalior 474011, Madhya Pradesh, India. Electronic address: prthvi.raj@utsouthwestern.edu.
authors.forename: Prithvi Raj
authors.initials: PR
authors.lastname: Sharma
authors.affiliation: Department of Anthropology (C.A.S), Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India. Electronic address: pkdas123@gmail.com.
authors.forename: P K
authors.initials: PK
authors.lastname: Das
authors.affiliation: National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: bame0200@mail.jnu.ac.in.
authors.forename: Rameshwar N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D049453:Luciferases, Bacterial; D049408:Luminescent Agents; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000276:immunology; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D049408:Luminescent Agents; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D049453:Luciferases, Bacterial
keywords: LD; Microsatellite; NOS2A; Tuberculosis