Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects.
Immunoregulatory eicosanoids have been implicated in protection from mycobacterial infection in cell and animal models. Recently, a study of the zebrafish embryo demonstrated that mutants of the lta4h gene, which encodes the leukotriene A4 hydrolase (LTA4H) enzyme of the eicosanoid pathway, have hypersusceptibility to Mycobacterium marinum infection. It also reported that heterozygosity at the two single nucleotide polymorphisms rs1978331 and rs2660898 located in introns of the LTA4H gene, a human homologue of lta4h, is associated with protection from pulmonary tuberculosis. To replicate this association we genotyped six LTA4H gene polymorphisms in samples from 3703 pulmonary tuberculosis patients and 5412 healthy controls collected in Russia. We found no evidence of the protective effect of heterozygosity at the polymorphisms rs1978331 and rs2660898 (P = 0.29 and 0.49) and no association of the alleles of any of the six polymorphisms (P = 0.13-0.81). These results suggest that common polymorphisms in the LTA4H gene do not play any major role in susceptibility to clinical pulmonary tuberculosis.
Department of Medicine, University of Cambridge, Cambridge, United Kingdom, Level 5, Addenbrookes Hospital, Hills road, Cambridge CB2 0QQ, United Kingdom.
James
J
Curtis
Liliya
L
Kopanitsa
Emma
E
Stebbings
Arran
A
Speirs
Olga
O
Ignatyeva
Yanina
Y
Balabanova
Vladyslav
V
Nikolayevskyy
Sven
S
Hoffner
Rolf
R
Horstmann
Francis
F
Drobniewski
Sergey
S
Nejentsev
D000818:Animals; D004195:Disease Models, Animal; D004851:Epoxide Hydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012426:Russia / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000235:genetics*; D014744:Vietnam / Q000453:epidemiology; D015027:Zebrafish
D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase