Genetic variants at 18q11.2 and 8q24 identified by genome-wide association studies were not associated with pulmonary tuberculosis risk in Chinese population

ObjectiveGenome-wide association study (GWAS) recently identified several susceptibility loci in ASAP1 gene on chromosome 8q24 for tuberculosis (TB) in a Russian population, but no relevant studies have been performed to validate these findings. In addition, previous GWAS in Ghana and Gambia found that the variant rs4331426 at 18q11.2 was a susceptibility locus for TB. However, the follow-up studies reported conflicting results. Herein, we investigated the contribution of genetic variants at 8q24 and 18q11.2 to TB in Chinese population.MethodsWe genotyped four genetic variants at 8q24 (rs10956514 and rs11774633) and 18q11.2 (rs4331426 and rs6507226) in a case–control study with 355 newly bacteriologically confirmed pulmonary TB cases and 395 healthy controls using TaqMan allelic discrimination assay. Subsequently, we conducted a meta-analysis including 4 reported studies in Chinese populations and our case–control study with a total of 3118 cases and 3226 controls to further evaluate the relationship between rs4331426 at 18q11.2 and TB risk.ResultsWe did not find significant association between genetic variants at 8q24 and risk of TB (rs10956514: OR = 0.89, 95%CI: 0.72–1.09, P = 0.253; rs11774633: OR = 0.86, 95%CI: 0.69–1.08, P = 0.206). We did not observe significant association for genetic variants at 18q11.2 (rs4331426: OR = 0.62, 95%CI: 0.34–1.14, P = 0.122; and rs6507226: OR = 0.98, 95%CI: 0.80–1.20, P = 0.853). Moreover, the pooled results from the Meta-analysis further supported that rs4331426 at 18q11.2 was not associated with TB risk in Chinese population (OR = 0.90, 95% CI: 0.63–1.29).ConclusionsOur findings indicate that TB risk-associated loci at 8q24 and 18q11.2 identified by GWAS from the other populations may not contribute to TB susceptibility in Chinese population.     

Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms

Background: Toll-like receptors (TLRs) are involved in the recognition of conserved microbial structures, leading to activation of an inflammatory response and formation of an adaptive immune response. Methods: Twenty-three polymorphisms in five TLR genes were genotyped in 729 tuberculosis cases and 487 healthy controls in a population-based case-control association study in a South African population. Results: We detected sex-specific associations for TLR8 polymorphisms, with rs3761624 (OR = 1.54, p < 0.001), rs3764879 (OR = 1.41, p = 0.011) and rs3764880 (OR = 1.42, p = 0.011) associated in females and rs3764879 (OR = 0.72, p = 0.013) and rs3764880 (OR = 0.75, p = 0.036) associated in males. Epistatic interactions between the TLR genes were investigated and the TLR1_rs4833095 polymorphism was shown to interact with TLR2_rs3804100 and (GT)_n microsatellite (p = 0.002) and alter susceptibility to TB. We also studied the role of TLRs in disease caused by different Mycobacterium tuberculosis genotypes in 257 tuberculosis cases, and identified associations between specific TLR polymorphisms and disease caused by specific strains. Conclusion: This study provides further evidence that the TLRs play an important role in the outcome of tuberculosis disease, and suggests a partial explanation for the male bias in tuberculosis ratios.     

Toll-like receptor 7 variations are associated with the susceptibility to HCV infection among Chinese females

Toll-like receptors 7 (TLR7) play a crucial role in provoking an immune response in HCV infection. We aimed to investigate whether single nucleotide polymorphisms (SNPs) of TLR7, including rs179009, rs179010 and rs179012, affect the outcomes of HCV infection among the Chinese population. A total of 1767 Chinese Han individuals were enrolled. The distribution of SNP frequencies among three groups with different outcomes of HCV infection was assessed, including healthy controls, cases with spontaneous clearance and cases with viral persistence. Then TLR7 mRNA expression and the production of IFN-α and IL-6 after TLR7 agonist Imiquimod stimulation in vitro were determined. Our results suggested that rs179009 GG genotype was significantly associated with a higher risk of the susceptibility to HCV infection among female subjects (OR = 2.42, 95% CI = 1.24–4.71, P = 0.01). Haplotype GCG was significantly associated with a high risk for HCV susceptibility (OR = 1.50, 95% CI = 1.11–2.03, P = 0.01) as compared with the reference haplotype ACG among females. In the functional research of rs179009, a lower IFN-α level was observed in GG genotype than in AA genotype (P = 0.032). Our data indicate that TLR7 rs179009 GG genotype and haplotype GCG were associated with an increased risk of the susceptibility to HCV infection among Chinese females, which may be due to the impaired IFN-α response.     

Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: A meta-analysis

ObjectiveToll-like receptor 4 (TLR4) plays a vital role in immunity to tubercle bacillus and its gene polymorphisms are supposed to affect tuberculosis susceptibility in some rather than all studies. Then, we integrated published data and performed a comprehensive meta-analysis to get more reliable estimations for the strength of associations between TLR4 gene polymorphisms and the risk of tuberculosis.MethodsWe systematically searched the electronic PubMed database for research articles about TLR4 gene polymorphisms and tuberculosis up to February 2012. Revman 5.0 software was adopted to conduct the meta-analysis. Crude odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated by either fixed-effects model or random-effects model.ResultsFinally, six case-control studies were identified, involving 1587 controls and 2110 patients. Overall, no significant associations were found between TLR4 gene Asp299Gly polymorphism and tuberculosis in the codominant models (GG vs AA: OR = 1.56, 95% CI = 0.76–3.21, P = 0.23; GA vs AA: OR = 1.01, 95% CI = 0.84–1.23, P = 0.89), the dominant model (GG + GA vs AA: OR = 1.04, 95% CI = 0.80–1.35, P = 0.75), the recessive model (GG vs GA + AA: OR = 1.55, 95% CI = 0.75–3.19, P = 0.24) and the allele model (G vs A: OR = 1.06, 95% CI = 0.81–1.40, P = 0.66). Similarly, no significant associations between TLR4 gene Thr399Ile and tuberculosis were observed (all P > 0.05).ConclusionsThe present meta-analysis suggests that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with the susceptibility of tuberculosis.     

Association of human leukocyte antigen DP/DQ gene polymorphisms with chronic hepatitis B in Chinese Han and Uygur populations

Several genome-wide association studies (GWAS) have shown that human leukocyte antigen (HLA) DP/DQ gene polymorphisms are associated with susceptibility to chronic hepatitis B virus (HBV) infection. We clarified the roles of the HLA-DP/DQ gene in HBV infection in different nationalities. Three single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277471, rs9277535 and rs9277542) and the SNP rs9272346 in HLA-DQ were studied. In total, 779 patients were recruited to this study, including 400 Chinese Han and 399 Uygurs. The rs9277535 variant genotypes were directly associated with HBV persistence compared to healthy controls in an additive model of the Chinese Han population (odds ratio [OR] = 1.88, 95% confidence interval [CI] = 1.03–3.41, P = 0.040), and in a recessive model of the Chinese female population (OR = 2.02, 95% CI = 1.26–3.24, P = 0.003). In addition, rs9277471 and rs9277542 variant genotypes significantly decreased the risk of HBV infection compared to healthy controls in an additive model of the Chinese Han population (OR = 0.53, 95% CI = 0.29–0.98, P = 0.042; OR = 0.53, 95% CI = 0.29–0.97, P = 0.039) and in a dominant model of the Chinese female population (OR = 0.50, 95% CI = 0.31–0.80, P = 0.004; OR = 0.49, 95% CI = 0.31–0.79, P = 0.003). The GG genotype of rs9277346 was associated with HBV infection in the Chinese Han population (additive model: OR = 0.38, 95%CI = 017–0.82, P = 0.014; recessive model: OR = 0.41, 95% CI = 0.19–0.86, P = 0.019) and in males (additive model: OR = 0.31, 95% CI = 0.14–0.65, P = 0.002; dominant model: OR = 0.65, 95% CI = 0.43–0.97, P = 0.034; recessive model: OR = 0.36, 95% CI = 0.18–0.73, P = 0.005). In addition, allele G of rs9277346 was marginally related to a reduction in risk for HBV infection in the Uygur population. Our study suggests that HLA-DP/DQ polymorphisms can affect susceptibility and resistance to HBV infection in Chinese populations, and are possibly linked to race and sex.     

Caractéristiques des centres de santé et conseils prénatals de préparation à la naissance

AimCounseling relating to birth preparedness is an essential component of the WHO Focused Antenatal Care model. During the antenatal visits, women should receive the information and education they need to make choices to reduce maternal and neonatal risks. The objective of this study conducted among women attending antenatal visits in rural Burkina Faso was to search for a link between the characteristics of the center delivering the health care and the probability of being exposed to information and advice relating to birth preparedness.MethodsA multilevel study was performed using survey data from women (n = 464) attending health centres (n = 30) in two rural districts in Burkina Faso (Dori and Koupela). The women were interviewed using the modified questionnaire of the Johns Hopkins Program for International Education in Gynecology and Obstetrics (JHPIEGO).ResultsWomen reported receiving advice about institutional delivery (72%), signs of danger (55%), cost of institutional delivery (38%) and advice on transportation in the event of emergency (12%). One independent factor was found to be associated with reception of birth preparedness advice: number of antenatal visits attended. Compared with women from Dori, women from Koupela were more likely to have received information on signs of danger (OR = 3.72; 95%CI: 1.26–7.89), institutional delivery (OR = 4.37; 95%CI: 1.70–10.14), and cost of care (OR = 3.01; 95%CI: 1.21–7.46). The reduced volume of consultations per day and the availability of printed materials significantly remain associated with information on the danger signs and with the institutional delivery advices. Comparison by center activity level showed that women attending health centers delivering less than 10 antenatal visits per day were more likely to receive information on signs of danger (OR = 2.63; 95%CI: 1.12–6.24) and to be advised about institution delivery (OR = 6.30; 95%CI: 2.47–13.90) compared to health centers delivering more than 20 antenatal visits per day. Women attending health centres equipped with printed materials (posters, illustrated documents) were more likely to receive information on signs of danger (OR = 4.25; 95%CI: 1.81–12.54) and be advised about institutional delivery (OR = 6.85; 95%CI: 3.17–14.77).ConclusionEfforts should be made to reach women with birth preparedness messages. Rural health centres in Burkna Faso need help to upgrade their organizational services and provide patients with printed materials so they can improve antenatal care delivery.     

Efficacy of a tailored PCR-guided triple therapy in the treatment of Helicobacter pylori infection

IntroductionResistance to clarithromycin and fluoroquinolones is increasing in many countries. We aimed to assess the efficacy of a tailored PCR-guided triple therapy versus an empirical triple therapy in the treatment of H. pylori infection.Patients and methodsFrench multicenter prospective open-label randomized study to assess H. pylori and resistance to clarithromycin and levofloxacin with GenoType HelicoDR® test. Patients of the control group were treated with empirical therapy of proton pump inhibitor (PPI), amoxicillin, and clarithromycin for 7 days. Patients of the experimental group with clarithromycin-susceptible strains, clarithromycin-resistant/levofloxacin-susceptible strains, and with clarithromycin-resistant/levofloxacin-resistant strains received tailored therapy of PPI, amoxicillin, and clarithromycin for 7 days, PPI, amoxicillin, and levofloxacin for 10 days, and PPI, amoxicillin, and metronidazole for 14 days, respectively. H. pylori eradication was assessed by ¹³C urea breath test at least 28 days after the end of treatment.ResultsWe included 526 patients: 260 (49.4%) were randomly assigned to empirical triple therapy and 266 (50.6%) to tailored therapy. Clarithromycin and levofloxacin resistances were 23.3% and 12.8%, respectively. Follow-up urea breath test was available for 415 (78.9%) patients. Tailored therapy was superior to empirical therapy in terms of eradication (85.5% vs. 73.1%, RR = 1.85, 95%CI [1.25–2.78], p = 0.003). Findings were consistent in the susceptibility analysis using multiple imputation (RR = 1.61, 95%CI [1.14–2.27], P = 0.003) and per-protocol analysis (RR = 1.89, 95%CI [0.25–2.78], p = 0.003).ConclusionIn a country with a high level of clarithromycin resistance, tailored PCR-guided therapy was superior to empirical triple therapy for H. pylori eradication (https://www.ClinicalTrials.gov: NCT01168063).     

Is the Beijing strain of Mycobacterium tuberculosis associated with cavitary lung disease?

We conducted a cross-sectional study to describe clinical characteristics of patients with pulmonary tuberculosis with and without evidence of pulmonary cavitation on chest radiography and assess whether cavitation is associated with infection with Mycobacterium tuberculosis Beijing strain. Cases were selected from the Tuberculosis Registry (January 1, 2008–November 1, 2011) of the Florida Department of Health (FDOH). Molecular characterization was performed by spoligotyping and MIRU-VNTR. We analyzed 975 cases, where 144 (14.8%) were infected with the Beijing strain. Cavitation was not associated with disease caused by the Beijing strain. Alcohol use (OR = 1.7; 95%CI: 1.249–2.313) was associated with increased risk of cavitation in the unadjusted analyses. Multivariable analyses showed that older age (⩾65 years) (OR = 0.5; 95%CI: 0.233–0.871), Hispanic ethnicity (OR = 0.6; 95%CI: 0.312–0.962), and co-infection with HIV (OR = 0.1; 95%CI: 0.068–0.295) demonstrated protective effects to cavitation. Understanding the factors associated with cavitation among pulmonary cases is essential toward improved tuberculosis management and control.     

Séroprévalence des marqueurs de l’infection chez les donneurs de sang à Niamey (Niger)

BackgroundThe study aimed to determine the seroprevalence of transfusion-transmitted infectious (TTI) markers for human immunodeficiency virus (HIV), hepatitis B and C viruses (HBV, HCV) and syphilis among blood donors in Niamey (Niger). The association between seroprevalence of ITT markers and sociodemographic characteristics of blood donors was investigated.MethodsA cross-sectional study was conducted in 2010 among 3213 blood donors. Data were collected from a pre-donation questionnaire and from laboratory tests results.ResultsThe male/female ratio was 4/1. Up to 18.1% of donations had at least one positive marker, in which 2.7% presented a positive test for two or more agents. A seroprevalence of 1.62% (95%CI: 1.21–2.12) was associated with HIV, 15.4% (13.9–16.7) with HBV, 1.18% (0.84–1.62) with HCV, and 0.47% (0.26–0.77) for blood samples reacted with RPR test for syphilis. The HIV seroprevalence was two-fold higher in family than in volunteer donors (OR = 2.15, 95%CI: 1.24–3.73). It was also higher in Rhesus D negative donors (OR = 2.40, 95%CI: 1.11–5.17). The hepatitis B surface antigen seroprevalence was significantly higher in males than females (OR = 1.85, 95%CI: 1.39–2.45) and in first time than in regular donors (P < 0.0001). The HCV seroprevalence was significantly higher in male donors (OR = 4.41, 95%CI: 1.06–18.4) and in donors from rural areas (OR = 4.09, 95%CI: 1.42–11.8). Syphilis marker was significantly associated with the marital status (higher seroprevalence in divorced donors, P = 0.0085).ConclusionPrevalence of TTI markers is high and national strategies for safe blood transfusion have to be strengthened. It is essential to recruit and maintain more volunteer donors, while females should be encouraged to donate blood.     

The CD14 −159C/T polymorphisms and the risks of tuberculosis: A meta-analysis

Previous studies about the association between CD14 −159C/T polymorphisms and the risks of tuberculosis (TB) have yielded conflicting results, and thus a meta-analysis was performed in order to provide a more accurate estimation. A computerized literature search with additional manual search was conducted for the relevant available studies. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated by either fixed-effects model or random-effects model based on heterogeneity test. A total of 8 eligible studies (1729 cases and 1803 controls) were included in the meta-analyses. Overall, a significant association between CD14 −159C/T polymorphism and TB risks was detected in the recessive model (TT vs. TC/CC, OR = 1.48, 95%CI 1.06–2.07). Significant associations were also detected in Asians (T vs. C, OR = 1.49, 95%CI 1.33–1.67; TT vs. CC, OR = 1.94, 95%CI 1.54–2.45; TT vs. TC/CC: OR = 1.86, 95%CI 1.57–2.20). In contrast, no significant association was detected in Caucasians in each genetic model. The subgroup analysis stratified by TB types showed a significant association between CD14 −159C/T polymorphism and pulmonary TB risks (T vs. C, OR = 1.51, 95%CI 1.01–2.26; TT vs. TC/CC, OR = 1.84, 95%CI 1.03–3.29), which did not reach statistically significance when the P values were Bonferroni adjusted to 0.025. No publication bias was detected in any comparisons. Collectively, the results of this meta-analysis suggest a possible association between CD14 −159C/T polymorphism and TB risks in Asians, but not in Caucasians. Well-designed case-control studies with larger sample size are needed to confirm these results.     

Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

BackgroundTLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.Materials and methodsA total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.ResultsThe TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).ConclusionsThe TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.     

Toll-like receptor 8 (TLR8) polymorphisms are associated with non-progression of chronic hepatitis C in HIV/HCV coinfected patients

Toll-like receptor 8 (TLR8) polymorphisms have been related to hepatitis C virus (HCV) infection. The aim was to estimate the association of TLR8 polymorphisms with HCV-related outcomes in HIV/HCV coinfected patients. We performed a cross-sectional study of 220 patients who underwent a liver biopsy. TLR8 polymorphisms were genotyped using GoldenGate® assay. The outcome variables were non-fibrosis (F0), mild-inflammation (A0/A1), and non-steatosis [fatty hepatocytes (FH) < 10%]. Logistic regression analysis was used to compare the outcome variables according to TLR8 polymorphisms. Four polymorphisms were analyzed (rs1013151, rs5744069, rs17256081 and rs3764880rs1013151). Female patients had higher frequency of TLR8 major alleles at rs17256081 and rs101315, and minor alleles at rs3764880 and rs5744069. Male patients had higher frequency of TLR8 minor alleles except for rs3764880, where major alleles were higher (p < 0.01). Two TLR8 polymorphisms (rs1013151 and rs5744069) were significantly associated with non-fibrosis (F0) [adjusted odds ratio (aOR) = 4.42 (95% of confidence interval (95%CI) = 1.54; 12.68) (p = 0.006) and aOR = 4.76 (95%CI = 1.69; 13.37) (p = 0.003); respectively]. When data were stratified by gender, rs1013151 and rs5744069 polymorphisms remained significant for male patients [adjusted odds ratio (aOR) = 4.49 (95%CI = 1.08; 18.62) (p = 0.039) and aOR = 6.17 (95%CI = 1.45; 26.20) (p = 0.014); respectively]. When data were stratified by major HCV genotypes, patients infected with HCV genotype 1 (GT1) had significant values for both rs1013151 and rs5744069 polymorphisms [aOR = 5.79 (95%CI = 1.44; 23.32) (p = 0.013) and aOR = 8.01 (95%CI = 2.16; 35.65) (p = 0.005); respectively]. Finally, none of the TLR8 polymorphisms were significantly associated with mild-inflammation or non-steatosis. In conclusion, TLR8 polymorphisms seem to be related to non-progression of liver fibrosis in HIV/HCV coinfected patients, particularly in males and those patients infected with GT1.     

SFRP1 variations influence susceptibility and immune response to Mycobacterium tuberculosis in a Chinese Han population

ObjectivesSFRP1 acts as a well-established inhibitory regulator of the Wnt signaling pathway, whose polymorphisms have been demonstrated to be associated with the risk of inflammation, infection as well as cancer. We verified the hypothesis that single nucleotide polymorphisms (SNPs) within SFRP1 gene are associated with susceptibility and clinical characteristics of tuberculosis disease in a Chinese Han population.MethodsSix candidate SNPs were genotyped using MassARRAY method in a case–control design (260 tuberculosis patients and 252 healthy controls). A comprehensive analysis of single locus including the genotypic, allelic frequencies and the genetic models, haplotypic construction as well as gene–gene interaction was conducted to investigate the relationships between SNPs and TB. Significant SNPs were further interrogated in relation to TB clinical features and host inflammatory status.ResultsGenotype frequencies of rs4736958 and rs7832767 within SFRP1 gene were significantly different (p = 0.011, p = 0.008, respectively) between tuberculosis group and control group. Subjects carrying C allele for rs4736958 showed a decreased tuberculosis risk (OR = 0.66, 95% CI = 0.51–0.87, p = 0.003), whereas individuals carrying rs7832767 T allele had a significant increased risk in tuberculosis susceptibility (OR = 1.32, 95% CI = 1.01–1.74, p = 0.046). Genetic model analysis revealed that dominant, co-dominant and recessive models of rs4736958 were associated with decreased susceptibility to tuberculosis (p all < 0.05), while the recessive and co-dominant models of rs7832767 were related to significantly increased risk for tuberculosis (p all < 0.05). There was a reduced tuberculosis risk in association with the haplotype CC (representing rs3242 and rs4736958) of SFRP1 (OR = 0.73, 95% CI = 0.56–0.96, p = 0.026). Further stratification analysis indicated that TB patients with genotype CT for rs4736958 were associated with higher CRP concentrations, and heterozygous patients (CT genotype) of rs7832767 trended towards greater ESR levels.ConclusionSNPs rs4736958 and rs7832767 of SFRP1 gene were significantly associated with tuberculosis susceptibility and might influence the expression levels of inflammatory markers of tuberculosis patients in a Chinese Han population.     

Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study

BackgroundDengue is a systemic viral infection that spreads to humans by the bite of infected Aedes mosquitoes. The secreted NS1 protein of dengue virus activates macrophages and human PBMCs via TLR4 and induce the release of pro-inflammatory cytokines which is responsible for the pathogenesis of disease. Mutations in TLR4 gene have been associated with the increased susceptibility to many viral, bacterial and parasitic diseases.ObjectiveTo study the impact of TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) gene polymorphisms with susceptibility to dengue infection.MethodsA total of 120 dengue infected (57; DHF/DSS and 63; DF) and 200 healthy controls were included in the study. TLR4 Asp299Gly and Thr399Ile gene polymorphisms was studied by PCR-RFLP. Expression of TLR4 mRNA was evaluated by rRT-PCR.ResultsIndividuals with heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms had increased susceptibility to dengue infection (OR-1.70, 95% CI = 1.01–2.86 P = 0.042 and OR-2.17, 95% CI = 1.10–4.28, P = 0.024, respectively). The frequency of Gly and Ile alleles were higher in dengue patients as compared to controls (OR-1.67, 95% CI = 1.05–2.64, P = 0.029 and OR-2.20, 95% CI = 1.19–4.07, P = 0.011, respectively). IIe/Gly haplotype was associated with the risk of the disease when compared with controls (OR = 3.15, 95% CI = 1.09–9.09, P = 0.035). The mRNA expression was higher in DF when compared with DHF/DSS and controls (P = 0.040 and 0.009, respectively).ConclusionA higher expression of TLR4 mRNA was associated with DF. The TLR4 Asp299Gly and Thr399Ile gene polymorphisms were associated with the susceptibility of dengue infection probably by altering the immune response.     

Interferon-γ (IFNG) microsatellite repeat and single nucleotide polymorphism haplotypes of IFN-α receptor (IFNAR1) associated with enhanced malaria susceptibility in Indian populations

Pro-inflammatory cytokines IFNγ and IFNα function through their cellular receptors IFNγR1 and IFNαR1, respectively to mediate immune processes during malaria infection. A total of 21 SNPs, 2 ins/del polymorphisms and a microsatellite repeat, selected on the basis of their reported association with infectious diseases including malaria in world populations, were analysed for association with Plasmodium falciparum malaria susceptibility in a case-control study with adult patients and ethnically-matched controls drawn from a disease meso- to hyperendemic and a nonendemic region of India. Among the five IFNG SNPs tested, an intron 3 and a 3′UTR SNP associated with disease in the endemic region. In addition, large (CA)_n repeats of IFNG intron 1 associated with protection from severe malaria in the endemic region (severe vs. control, odds ratio = 0.21, 95% CI = 0.08–0.52, P = 1.3 × 10⁻⁴). The TA11CAG haplotype (rs2069705 T/C, rs2430561 A/T, rs3138557 (CA)_n, rs2069718 T/C, rs2069727 A/G, rs2069728 G/A) carrying a short CA₁₁ repeat also exhibited very strong association with severe malaria, particularly in the endemic region (severe vs. control, OR = 14.56, 95% CI = 3.39–85.81, P = 3 × 10⁻⁵). One SNP each from the IFNA8 and IFNA17 of IFNA gene cluster had a protective effect in the non-endemic region but not in the endemic region. A promoter and an intron 2 SNP of IFNAR1 were risk factors for disease and the IFNAR1 haplotype GCCAGG (rs2843710 C/G, rs2850015 C/T, +6993 C/T, rs2243594 A/G, rs1012335 G/C, rs2257167 G/C) carrying both the risk alleles strikingly associated with disease manifestation in the endemic region (severe vs. control, OR = 27.14, 95% CI = 3.12–1254, P = 2 × 10⁻⁵; non-severe vs. control, OR = 61.87, 95% CI = 10.08–2521, P = 1 × 10⁻⁸). The data indicates dissimilar contribution of cytokine and cytokine receptor variants to disease in populations residing in areas of differential malaria endemicity.     

Inicio de relaciones sexuales con penetración y factores asociados en chicos y chicas de México de 14-19 años de edad con escolarización en centros públicos

ObjectiveTo estimate the mean age of sexual intercourse debut (SID) and associated family and individual factors in 14-19-year-olds of both sexes in the 32 states of Mexico in 2007.MethodsA cross-sectional study was conducted of a representative sample of 9,893 students aged between 14 and 19 years old. The data were collected through a self-administered, anonymous and voluntary questionnaire. Logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (95%CI) by category: no SID, SID at 10-15 years and SID at 16-19 years.ResultsThe national mean age of SID was 16 years, being 15 years for boys (95%CI: 15.88-16.11) and 16 years for girls (95%CI: 15.26-15.42). Factors associated with SID in boys were disadvantaged socioeconomic level (OR = 0.66; 95%CI: 0.46-0.94), living with parents (OR = 0.65; 95%CI: 0.56-0.75), less offensive communication between parents and boys/girls (OR = 0.66; 95%CI: 0.57-0.77), and high social self-esteem (OR = 1.68; 95%CI: 1.35-1.77). Factors associated with SID in girls were traditional gender beliefs (OR = 0.49; 95%CI: 0.32-0.74), high depressive symptoms (OR = 1.88; 95%CI: 1.19-2.99), and high family self-esteem (OR= 0.50; 95%CI: 0.38-0.65).ConclusionsIn Mexico, SID occurred early in boys. In addition, the findings of this study show that in Mexico, the age of SID and associated factors differ in boys and girls. The age of SID is strongly influenced by gender and cultural beliefs.     

The effect of body mass index (BMI) and gestational weight gain on adverse obstetrical outcomes in pregnancies following assisted reproductive technology as compared to spontaneously conceived pregnancies

ObjectiveTo compare the effect of pre-pregnancy body mass index (BMI) and inappropriate gestational weight gain (GWG) on adverse obstetrical outcomes among women undergoing assisted reproductive technology (ART) treatments as compared to spontaneously-conceived (SC) pregnancies.MethodsThis prospective cohort study included 1058 pregnant women from two medical centres; 504 women who conceived following ART treatments and 554 who conceived spontaneously. The women were recruited at 8 weeks of gestation and follow-up telephone interviews were conducted 6 weeks after delivery. Obstetrical outcomes included pregnancy hypertension, gestational diabetes (GD), low birth weight (LBW) (<2500 g) and small for gestational age (SGA). Multivariate analyses were used to assess the effect of pre-pregnancy BMI and inappropriate GWG on these obstetrical outcomes adjusted for risk factors.ResultsThe effect of pre-pregnancy BMI and inappropriate GWG on adverse obstetrical outcomes did not differ between ART and SC pregnancies. Pre-pregnancy obesity was found to be associated with increased risk for pregnancy hypertension (OR = 2.16; 95%CI 1.16–4.03), GD (OR = 2.89; 95%CI 1.61–5.17), caesarian section (OR = 1.77; 95%CI 1.10–2.85) and SGA (OR = 1.91; 95%CI 1.05–3.46). GWG below recommendations was associated with increased risk for GD (OR = 1.73; 95%CI 1.06–2.82) and SGA (OR = 1.69; 95%CI 1.17–2.40) while GWG above recommendations was associated with increased risk for pregnancy hypertension (OR = 1.77; 95%CI 1.02–3.06).ConclusionsPre-pregnancy obesity and inappropriate GWG were associated with adverse obstetrical outcomes in both ART and SC pregnancies. Emphasis should be given on the importance of an optimal pre-pregnancy BMI and appropriate GWG during pregnancy.     

Factors associated with treatment failure after advice from infectious disease specialists

ObjectiveRisk factors associated with treatment failure after the infectious disease specialist's (IDS) advice remain unknown. We aimed to identify these risk factors.MethodsWe included patients hospitalized in our tertiary care center who consulted an infectious disease specialist between January 2013 and April 2015. Treatment failure was defined by a composite criterion: signs of sepsis beyond Day 3, ICU admission, or death. Treatment success was defined by the patient's sustained clinical improvement.ResultsA total of 240 IDS recommendations were made. Diagnosis was changed for 64 patients (26.7%) and 50 patients experienced treatment failure after the IDS advice. In multivariate analysis, compliance with the IDS advice was associated with a higher rate of success (OR = 0.09, 95%CI [0.01–0.67]). Variables associated with treatment failure in the multivariate analysis were Charlson comorbidity score at admission (OR = 1.24, 95%CI [1.03–1.50]), a history of infection or colonization with multidrug-resistant bacteria (OR = 8.27, 95%CI [1.37–49.80]), and deterioration of the patient's status three days after the IDS advice (OR = 12.50, 95%CI [3.16–49.46]).ConclusionReassessing IDS recommendations could be interesting for specific patients to further adapt and improve them.     

The polymorphisms of MSH6 gene are associated with AIDS progression in a northern Chinese population

It has been reported that DNA repair genes play an important role in HIV-1 infection and AIDS progression. One DNA repair pathway, the mismatch repair (MMR) is associated with a wide variety of tumors. However, the role of single nucleotide polymorphisms (SNPs) in the MMR genes and their importance in HIV-1 infection and AIDS progression remain unclear. In the present study, 479 HIV-1-infected and 487 healthy individuals from northern China were genotyped for nine SNPs in the MSH2 gene (rs13019654, rs4608577, rs4952887, rs6726691, rs10191478, rs12999145, rs1981929, rs2042649, rs2303428) and five SNPs in the MSH6 gene (rs2348244, rs3136245, rs3136329, rs2072447, rs7562048). Our results showed that the rs7562048 G allele frequency was significantly higher in the cases with the CD4⁺ T-lymphocyte count < 200 cells/μl than those with > 200 cells/μl (P = 0.001, OR = 1.811, 95% CI 1.255–2.614), which is in agreement with the result of the Bonferroni correction. The frequencies of the rs2348244 C allele and rs3136245 T allele were higher in the cases at clinical phase IV than those at clinical phase I + II + III (P = 0.026, OR = 1.591, 95% CI 1.056–2.398 and P = 0.019, OR = 1.749, 95% CI 1.096–2.791, respectively); however, this difference is not supported by the Bonferroni correction. There were no significant differences in the frequency of allele, genotype and haplotype of the 14 SNPs between HIV-1-infected individuals and healthy controls (P > 0.05). These results suggest that the rs7562048 is associated with the clinical features and that the MSH6 gene polymorphisms likely play an important role in the progression of AIDS in the northern Chinese population.