title: Interferon-gamma receptor 1 promoter polymorphisms: population distribution and functional implications.
abstract: Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polymorphisms (SNPs) were detected in the IFNGR1 MPR. The three ethnic groups showed different SNP distribution patterns, but no significant differences were detected between mycobacterial cases and controls. Two polymorphisms were found in all populations (G-611A, T-56C). We cloned the four allelic variants (var) of haplotype G-611A/T-56C into a luciferase reporter vector and determined their promoter activity. Polymorphisms at position -611 had a stronger effect on the promoter activity than those at position -56, and constructs carrying G-611 produced a stronger promoter activity than -611A constructs. The IFNGR1 MPR is a polymorphic region with at least two SNPs influencing its activity, but these are not associated with increased mycobacterial susceptibility.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, DHHS, Bethesda, MD 20892-1886, USA.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Rachel
authors.initials: R
authors.lastname: Sullivan
authors.forename: Balasz
authors.initials: B
authors.lastname: Enyedi
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Yim
authors.forename: James L
authors.initials: JL
authors.lastname: Cook
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D016015:Logistic Models; D008297:Male; D009169:Mycobacterium tuberculosis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA; D014162:Transfection; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D004247:DNA; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor