Association of Leukotriene A4 Hydrolase polymorphisms and risk of extrapulmonary tuberculosis

Abstract

Genetic risk assessment of tuberculosis development and genotypic variation influence the gene and protein expression of leukotriene A4 hydrolase (LTA4H) at various sites of tuberculosis. The relationship between the genotype and phenotype of LATH4A was investigated in relation to the genetic risk assessment of extrapulmonary tuberculosis (EPTB). This study included 137 patients with EPTB and age-sex-matched 137 normal controls of the same ethnicity. LTA4H genotyping was performed using restriction fragment polymorphisms (RFLP) and protein level was analyzed using enzyme-linked immunosorbent assay (ELISA). The LTAH4 (rs.197833A/G) AG (codominant) and GG (recessive) genotypes showed 1.86 and 1.88-fold higher risks (p=0.0004 and p<0.0001 respectively) of developing EPTB. LTA4H (rs.2660898 T/G) TG (codominant) and GG (recessive) genotypes significantly increased the risk (OR:1.69, p=0.0001 and OR;1.77 p=0.008 respectively) of EPTB. Similarly, LTA4H (rs. 2540474) AG (codominant) and GG (recessive) genotypes (OR; 1.58 95% CI:1.22- 2.04, p<0.0001; OR, 1.86; 95%CI 1.37-2.52, p<0.0001) increased the risk of developing ETTB. The LTB4 protein levels were significantly higher in EPTB cases (mean ± SD; 3096.10±1287.6 pg/mL) than in controls (2304.50±644.15 pg/mL) (p<0.0001). LTA4H recessive variants influence protein levels (functional genetics), resulting in risk of EPTB.