title: Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype.
abstract: BACKGROUND
  Emerging evidence suggests that Mycobacterium tuberculosis (Mtb) lineage and host ethnicity can determine tuberculosis (TB) clinical disease patterns but their relative importance and interaction are unknown.
  
  
  METHODS
  We evaluated prospectively collected TB surveillance and Mtb strain typing data in an ethnically heterogeneous UK population. Lineage assignment was denoted using 15-loci mycobacterial interspersed repetitive units containing variable numbers of tandem repeats (MIRU-VNTR) and MIRU-VNTRplus. Geographical and ethnic associations of the six global Mtb lineages were identified and the influence of lineage and demographic factors on clinical phenotype were assessed using multivariate logistic regression.
  
  
  RESULTS
  Data were available for 1070 individuals with active TB which was pulmonary only, extrapulmonary only and concurrent pulmonary-extrapulmonary in 52.1%, 36.9% and 11.0% respectively. The most prevalent lineages were Euro-American (43.7%), East African Indian (30.2%), Indo-Oceanic (13.6%) and East Asian (12.2%) and were geo-ethnically restricted with, for example, Indian subcontinent ethnicity inversely associated with Euro-American lineage (OR 0.23; 95% CI 0.14 to 0.39) and positively associated with the East African-Indian lineage (OR 4.04; 95% CI 2.19 to 7.45). Disease phenotype was most strongly associated with ethnicity (OR for extrathoracic disease 21.14 (95% CI 6.08 to 73.48) for Indian subcontinent and 14.05 (3.97 to 49.65) for Afro-Caribbean), after adjusting for lineage. With East Asian lineage as the reference category, the Euro-American (OR 0.54; 95% CI 0.32 to 0.91) and East-African Indian (OR 0.50; 95% CI 0.29 to 0.86) lineages were negatively associated with extrathoracic disease, compared with pulmonary disease, after adjusting for ethnicity.
  
  
  CONCLUSIONS
  Ethnicity is a powerful determinant of clinical TB phenotype independently of mycobacterial lineage and the role of ethnicity-associated factors in pathogenesis warrants investigation.
authors.affiliation: Tuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Manish
authors.initials: M
authors.lastname: Pareek
authors.forename: Jason
authors.initials: J
authors.lastname: Evans
authors.forename: John
authors.initials: J
authors.lastname: Innes
authors.forename: Grace
authors.initials: G
authors.lastname: Smith
authors.forename: Suzie
authors.initials: S
authors.lastname: Hingley-Wilson
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Lougheed
authors.forename: Saranya
authors.initials: S
authors.lastname: Sridhar
authors.forename: Martin
authors.initials: M
authors.lastname: Dedicoat
authors.forename: Peter
authors.initials: P
authors.lastname: Hawkey
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa / Q000208:ethnology; D000569:Americas / Q000208:ethnology; D001208:Asia / Q000208:ethnology; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D020071:Interspersed Repetitive Sequences; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D010802:Phylogeny; D011446:Prospective Studies; D014376:Tuberculosis / Q000208:ethnology* / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000382:microbiology; D006113:United Kingdom / Q000453:epidemiology; D044465:White People; D055815:Young Adult