RGD Reference Report - NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.

Authors: Velez, DR  Hulme, WF  Myers, JL  Weinberg, JB  Levesque, MC  Stryjewski, ME  Abbate, E  Estevan, R  Patillo, SG  Gilbert, JR  Hamilton, CD  Scott, WK 
Citation: Velez DR, etal., Hum Genet. 2009 Nov;126(5):643-53. Epub 2009 Jul 3.
RGD ID: 4144122
Pubmed: PMID:19575238   (View Abstract at PubMed)
PMCID: PMC2881538   (View Article at PubMed Central)
DOI: DOI:10.1007/s00439-009-0713-y   (Journal Full-text)

Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR = 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate correction for multiple comparisons (q* = 0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NOS2Humanpulmonary tuberculosis  IAGP DNA:SNPs:multiple (human)RGD 
Nos2Ratpulmonary tuberculosis  ISONOS2 (Homo sapiens)DNA:SNPs:multiple (human)RGD 
Nos2Mousepulmonary tuberculosis  ISONOS2 (Homo sapiens)DNA:SNPs:multiple (human)RGD 
TLR4Humanpulmonary tuberculosis susceptibilityIAGP DNA:SNP:intron: rs5030729 (human)RGD 
Tlr4Ratpulmonary tuberculosis susceptibilityISOTLR4 (Homo sapiens)DNA:SNP:intron: rs5030729 (human)RGD 
Tlr4Mousepulmonary tuberculosis susceptibilityISOTLR4 (Homo sapiens)DNA:SNP:intron: rs5030729 (human)RGD 
IFNGR1Humantuberculosis  IAGP  RGD 
Ifngr1Rattuberculosis  ISOIFNGR1 (Homo sapiens) RGD 
Ifngr1Mousetuberculosis  ISOIFNGR1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifngr1  (interferon gamma receptor 1)
Nos2  (nitric oxide synthase 2)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Ifngr1  (interferon gamma receptor 1)
Nos2  (nitric oxide synthase 2, inducible)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
IFNGR1  (interferon gamma receptor 1)
NOS2  (nitric oxide synthase 2)
TLR4  (toll like receptor 4)


Additional Information