TY - JOUR
T1 - Association of Leukotriene A4 Hydrolase with Tuberculosis Susceptibility Using Genomic Data in Portugal
AU - Rito, Teresa
AU - Ferreira, Joana
AU - Cavadas, Bruno
AU - Soares, Pedro
AU - Oliveira, Olena
AU - Richards, Martin B.
AU - Duarte, Raquel
AU - Pereira, Luísa
AU - Correia-Neves, Margarida
N1 - Brief Report
PY - 2019/12/4
Y1 - 2019/12/4
N2 - Leukotriene A4 hydrolase (LTA4H) is a key enzyme in the eicosanoid pathway. lta4h locus polymorphisms have previously been linked to tuberculosis (TB) susceptibility and disease outcome in a Vietnamese dataset, but further studies suggested that those results were poorly reproducible. We, therefore, compared the full set of variants (113 SNPs) within the gene in a Portuguese dataset of 112 TB patients and 120 controls, using both the frequency of SNPs and haplotypes, in order to assess their association with TB susceptibility. Although we obtained no significant differences between the TB patients and the control group, linkage analysis showed that an extensively typed polymorphism, rs17525495, was associated with 21 other SNPs, all displaying evidence of association to lower LTA4H expression. While the derived alleles of these SNPs showed a moderately higher frequency in the TB group, differences were not significant. In contrast to Asian populations, where these SNPs are much more frequent, the low frequencies of candidate SNPs in Europeans render them less pertinent in a public health context. Consequently, the typing of specific polymorphisms as a strategy to establish preventive measures and differential TB drug treatments is important but needs to take into consideration that haplotypic background and structure can be substantially different in distinct geographic regions.
AB - Leukotriene A4 hydrolase (LTA4H) is a key enzyme in the eicosanoid pathway. lta4h locus polymorphisms have previously been linked to tuberculosis (TB) susceptibility and disease outcome in a Vietnamese dataset, but further studies suggested that those results were poorly reproducible. We, therefore, compared the full set of variants (113 SNPs) within the gene in a Portuguese dataset of 112 TB patients and 120 controls, using both the frequency of SNPs and haplotypes, in order to assess their association with TB susceptibility. Although we obtained no significant differences between the TB patients and the control group, linkage analysis showed that an extensively typed polymorphism, rs17525495, was associated with 21 other SNPs, all displaying evidence of association to lower LTA4H expression. While the derived alleles of these SNPs showed a moderately higher frequency in the TB group, differences were not significant. In contrast to Asian populations, where these SNPs are much more frequent, the low frequencies of candidate SNPs in Europeans render them less pertinent in a public health context. Consequently, the typing of specific polymorphisms as a strategy to establish preventive measures and differential TB drug treatments is important but needs to take into consideration that haplotypic background and structure can be substantially different in distinct geographic regions.
KW - Eicosanoids
KW - Gene polymorphisms
KW - Genomics
KW - Infectious diseases
KW - Tuberculosis (TB) susceptibility
UR - http://www.scopus.com/inward/record.url?scp=85078610005&partnerID=8YFLogxK
U2 - 10.3390/microorganisms7120650
DO - 10.3390/microorganisms7120650
M3 - Article
AN - SCOPUS:85078610005
VL - 7
JO - Microorganisms
JF - Microorganisms
SN - 2076-2607
IS - 12
M1 - 650
ER -