Polymorphism in cathelicidin gene (CAMP) that alters Hypoxia‐inducible factor (HIF‐1α::ARNT) binding is not associated with tuberculosis

Abstract

Polymorphisms in the CAMP gene (cathelicidin) have not been tested in tuberculosis susceptibility. We tested polymorphisms rs9844812 (HIF-1α::ARNT binding site) and rs56122065 (CAMP) plus rs1800972 (DEFB1). SNP rs1800972 was associated with extrapulmonary tuberculosis (EPTB) in a codominant model (genotype CG, P = 0.037, OR 4.82; 95% CI: 0.92-47.42; statistical power, 82%), but not PTB (P = 0.101) in a Mexican population.

DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population

“…Our findings have discrepancies with the results obtained by Wu et al 8 on Han population and by Lopez Campos et al 37 in Mexicans: we can hypothesize that the differences could be, at least in part, due to ethnicity, since the frequencies DEFB1 SNPs vary in different populations. According to the NCBI and HapMap databases, 38 for −52 SNP (rs1799946) the frequency of the ancestral allele is 0.64 in European (CEU), 0.56 in Sub-Sahara African (YRI) and 0.40 in Asian (HCB); the frequency of ancestral allele of −44 SNP (rs1800972) is 0.26 in European (CEU), 0.04 in Sub-Sahara African (YRI) and 0.12 in Asian (HCB); for −20 SNP (rs11362), the frequency is 0.61 in European (CEU), 0.60 in Sub-Sahara (YRI) and 0.71 in Asian (HCB).…”

“…However, we cannot exclude, that the lack of association reported in our study, could be due to the limited sample size; the power of our study (post hoc Power ≤ 0.5) indicates that not finding an association between SNPs with TB development, could be due to a type II error. This is a strong limitation of our study, and seeing that also the works of Wu et al 8 and Lopez Campos et al 37 suffer the same sample size problem, we are convinced that any further study dealing with association between defensins gene polymorphism and TB, should enroll greater number of patients, may be joining several research groups, in order to achieve better statistical power to provide a definitive answer on the role of defensins in susceptibility to TB.…”

“…In a recent work, performed on a limited number of Mexican patients (27 with pulmonary TB and 16 with extrapulmonary TB) and controls ( n = 49), López Campos et al 37 described an association between DEFB1 −44C>G SNP (CG genotype in a codominant genetic model) and susceptibility to extrapulmonary TB, but not with the pulmonary TB, hypothesizing a role for hBD-1 in the fight against M. tuberculosis outside the lung.…”

“…Additionally, in the Han Chinese population no linkage disequilibrium was detected ( D ′ < 0.5) 8 and as a consequence comparing DEFB1 haplotype results with our findings has not been possible. Moreover, when looking at the Mexican population it has to be remarked that the study of Lopez Campos et al 37 just analyzed one DEFB1 SNP −44C>G and other SNPs in cathelicidin encoding CAMP gene. So, it was not possible to compare our DEFB1 haplotypes with the results reported for Mexican patients.…”

Inverse Correlation between IL-10 and HIF-1α in Macrophages Infected with Histoplasma capsulatum

“…HIF-1α evokes direct killing of many pathogenic microbes by primary mediators such as reactive oxygen species, nitric oxide (NO), and antimicrobial peptides (22–25). Direct targets of HIF-1α in myeloid cells include the pro-inflammatory molecules TNF-α, IL-12, and CCL2 as well as the anti-inflammatory IL-10 (26–29). …”