title: Influence of candidate susceptibility genes on tuberculosis in a high endemic region.
abstract: Genetic susceptibility towards clinical tuberculosis has been proposed in several population studies. We investigated whether polymorphisms in the candidate genes encoding solute carrier 11a1 protein (SLC11A1 formerly NRAMP1), mannose-binding lectin (MBL2) and Vitamin D receptor (VDR) were associated with tuberculosis in an East-African setting. Four hundred and forty-three culture positive pulmonary tuberculosis patients and 426 controls from Mwanza district in the northern part of Tanzania were prospectively included. Polymorphisms in the candidate genes were detected by different PCR-based techniques. A significant association between pulmonary tuberculosis and a microsatellite marker in the 5'(CA)n locus in the SLC11A1 gene compared with controls (38% versus 30% odds ratio 1.45, 95% CI: 1.06-1.9, P=0.014) was observed. The association was apparent only in HIV negative tuberculosis patients. No association with tuberculosis was seen with 3 other SLC11A1 loci investigated, which previously have been associated with tuberculosis in other populations or with MBL2 and VDR polymorphisms. The tuberculosis associated microsatellite marker was situated on different SLC11A1 haplotypes. In this cohort a microsatellite marker in the 5'(CA)n locus situated in the SLC11A1 gene was associated with tuberculosis. The observed association was seen only in HIV negative patients suggesting that this genetic susceptibility for tuberculosis may be surpassed by co-infections.
authors.affiliation: Tissue Typing Laboratory of the Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Søborg
authors.forename: Aase Bengaard
authors.initials: AB
authors.lastname: Andersen
authors.forename: Nyagosya
authors.initials: N
authors.lastname: Range
authors.forename: Wabyahe
authors.initials: W
authors.lastname: Malenganisho
authors.forename: Henrik
authors.initials: H
authors.lastname: Friis
authors.forename: Pascal
authors.initials: P
authors.lastname: Magnussen
authors.forename: Mansuet M
authors.initials: MM
authors.lastname: Temu
authors.forename: John
authors.initials: J
authors.lastname: Changalucha
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics; D003710:Demography; D005260:Female; D005796:Genes; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018023:HIV Seronegativity / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D013636:Tanzania / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology* / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D037601:Mannose-Binding Lectin; D018167:Receptors, Calcitriol; D000099173:Natural Resistance-associated Macrophage Protein 1; C445619:MBL2 protein, human