Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population

Background: The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods: We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results: We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Conclusions: Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians

Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City

Objective To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico

Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers

Open Access

Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican populatio

Results of the Implementation of a Pilot Model for the Bidirectional Screening and Joint Management of Patients with Pulmonary Tuberculosis and Diabetes Mellitus in Mexico

<div><p>Background</p><p>Recently, the World Health Organisation and the International Union Against Tuberculosis and Lung Disease published a Collaborative Framework for the Care and Control of Tuberculosis (TB) and Diabetes (DM) (CFTB/DM) proposing bidirectional screening and joint management.</p><p>Objective</p><p>To evaluate the feasibility and effectiveness of the CFTB/DM in Mexico. <b>Design</b>. Prospective observational cohort. <b>Setting</b>. 15 primary care units in 5 states in Mexico. <b>Participants</b>: Patients aged ≥20 years diagnosed with DM or pulmonary TB who sought care at participating clinics. <b>Intervention</b>: The WHO/Union CFTB/DM was adapted and implemented according to official Mexican guidelines. We recruited participants from July 2012 to April 2013 and followed up until March 2014. Bidirectional screening was performed. Patients diagnosed with TB and DM were invited to receive TB treatment under joint management. <b>Main outcome measures</b>. Diagnoses of TB among DM, of DM among TB, and treatment outcomes among patients with DM and TB.</p><p>Results</p><p>Of 783 DM patients, 11 (1.4%) were unaware of their TB. Of 361 TB patients, 16 (4.4%) were unaware of their DM. 95 TB/DM patients accepted to be treated under joint management, of whom 85 (89.5%) successfully completed treatment. Multiple linear regression analysis with change in HbA1c and random capillary glucose as dependent variables revealed significant decrease with time (regression coefficients (β)  = −0.660, (95% confidence interval (CI), −0.96 to −0.35); and β = −1.889 (95% CI, −2.77 to −1.01, respectively)) adjusting by sex, age and having been treated for a previous TB episode. Patients treated under joint management were more likely to experience treatment success than patients treated under routine DM and TB programs as compared to historical (adjusted OR (aOR), 2.8, 95%CI 1.28–6.13) and same period (aOR 2.37, 95% CI 1.13–4.96) comparison groups.</p><p>Conclusions</p><p>Joint management of TB and DM is feasible and appears to improve clinical outcomes.</p></div

Comparison of the sociodemographic characteristics and treatment outcome of patients with TB/DM diagnosed and treated in the same clinics from June 2009 to June 2012 (historical control) and in the same municipalities but different clinics from July 2012 to April 2013 (same period control), as compared to study population (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico).

<p>*Pearson's chi-squared test;</p><p>**Binomial test;</p>†<p>Mann-Whitney U test;</p>‡<p>As compared to study population. TB = Tuberculosis; DM = Diabetes mellitus; IQR = Interquartile range.</p><p>Comparison of the sociodemographic characteristics and treatment outcome of patients with TB/DM diagnosed and treated in the same clinics from June 2009 to June 2012 (historical control) and in the same municipalities but different clinics from July 2012 to April 2013 (same period control), as compared to study population (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico).</p

Flowchart of the bidirectional screening for TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).

<p>Flowchart of the bidirectional screening for TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).</p

Characteristics of the DM patients who were screened for TB (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).

<p>*Chi-squared test;</p><p>**U Mann-Whitney test; TB, Tuberculosis; DM, Diabetes mellitus; IQR, interquartile range; BMI, Body mass index.</p><p>Characteristics of the DM patients who were screened for TB (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).</p

Characteristics of patients with TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).

†<p>Chi-squared test.</p>‡<p>At least one of the following complications: retinopathy, hypertension, renal disease, renal failure, diabetic foot, obesity, neuropathy (mono or polyneuropathy), visceral neuropathy (diarrhoea, erectile dysfunction, etc.), urinary albumin, chest pain or other.</p>¶<p>Mann–Whitney test. TB, Tuberculosis; DM, Diabetes mellitus; IQR, interquartile range; BMI, Body mass index.</p><p>Characteristics of patients with TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).</p

Robust random effects linear regression for longitudinal data with change in HbA1c, fasting serum glucose and random capillary glucose as dependent variable among patients with TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).

<p>TB =  Tuberculosis; DM =  Diabetes mellitus; 95% CI = 95% Confidence interval;</p><p>*p<0.05,</p><p>**p<0.001.</p><p>Robust random effects linear regression for longitudinal data with change in HbA1c, fasting serum glucose and random capillary glucose as dependent variable among patients with TB and DM (Tijuana, Ciudad Juarez, Reynosa, Guadalupe and Zapopan, Mexico, 2013).</p