Polymorphisms in the CISH gene are associated with susceptibility to tuberculosis in the Chinese Han population

A recent multi-center case–control study identified several single nucleotide polymorphisms (SNPs) within the cytokine-inducible SRC homology 2 domain (CISH) gene that are associated with susceptibility to tuberculosis (TB) in both African and Asian populations. To acquire a more robust and well-powered estimate of the putative influence of these SNPs on TB susceptibility, we conducted a well-designed case–control study in the Chinese Han population. We genotyped 3 previously identified SNPs within CISH in 600 patients with pulmonary TB and 618 healthy controls, and we calculated the pooled P-values and ORs of several studies that have also been conducted in the Chinese populations. The results of the case–control study showed that the C allele of rs2239751 and the T allele of rs414171 are associated with TB susceptibility, and this association exists only in women and young adults. The pooled analysis indicated that both SNPs are significantly associated with TB in the global populations and Chinese populations. The current study confirms that variants of CISH are associated with susceptibility to TB, suggesting that negative regulators of cytokine signaling may have a role in immunity against TB infection. We hypothesize that CISH and estrogen may interact in the cytokine-dependent regulation of the immune system.     

Allopatric tuberculosis host–pathogen relationships are associated with greater pulmonary impairment

BackgroundHost pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. It remains unclear if host–pathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. We sought to examine the association between allopatric and sympatric phylogenetic Mycobacterium tuberculosis lineages and pulmonary impairment after tuberculosis (PIAT).MethodsPulmonary function tests were performed on patients 16 years of age and older who had received ⩾20 weeks of treatment for culture-confirmed M. tuberculosis complex. Forced Expiratory Volume in 1 min (FEV1) ⩾80%, Forced Vital Capacity (FVC) ⩾80% and FEV1/FVC >70% of predicted were considered normal. Other results defined pulmonary impairment. Spoligotype and 12-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were used to assign phylogenetic lineage. PIAT severity was compared between host–pathogen relationships which were defined by geography and ethnic population. We used multivariate logistic regression modeling to calculate adjusted odds ratios (aOR) between phylogenetic lineage and PIAT.ResultsSelf-reported continental ancestry was correlated with Mycobacterium. tuberculosis lineage (p < 0.001). In multivariate analyses adjusting for phylogenetic lineage, age and smoking, the overall aOR for subjects with allopatric host–pathogen relationships and PIAT was 1.8 (95% confidence interval [CI]: 1.1, 2.9) compared to sympatric relationships. Smoking >30 pack-years was also associated with PIAT (aOR: 3.2; 95% CI: 1.5, 7.2) relative to smoking <1 pack-years.ConclusionsPIAT frequency and severity varies by host–pathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatric–host–pathogen relationship were more likely to have PIAT than patients with disease from sympatric–host–pathogen relationship infection. Further study of this association may identify ways that treatment and preventive efforts can be tailored to specific lineages and racial/ethnic populations.     

NRAMP1和SP110基因多态性与蒙古族结核病易患的关系

目的 探讨NRAMP1基因rs17235409A/G、NRAMP1基因rs17235416TGTG/(-)和Sp110基因rs3948464C/T位点（以下简称NRAMP1rs17235409、NRAMP1rs17235416、SP110rs3948464）基因多态性与蒙古族结核病易患的关系。方法 采用病例-对照研究,收集蒙古族132例结核病患者和108例健康体检者静脉血,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法检测3个位点基因分型,运用卡方检验、广义多因子降维法(Generalized Multifactor Dimensionality Reduction,GMDR)分析NRAMP1和Sp110基因多态性及交互作用与结核病易患的关系。 结果 (1)病例组和对照组NRAMP1rs17235409位点GG型,GA型,AA型和NRAMP1rs17235416位点TGTG/TGTG型,TGTG/(-)型,(-)/(-)型基因频率分别为66.67%,30.30%,3.03% vs 86.11%,12.96%,0.93%和60.61%,33.33%,6.06% vs 80.55%,18.52%,0.93%,2个位点基因型与等位基因型在两组的构成均存在差异(〖XC五号.EPS;P〗=12.178,〖XC五号.EPS;P〗=12.462;〖XC五号.EPS;P〗=11.935,〖XC五号.EPS;P〗=13.193,均P＜0.05)。(2)Sp110rs3948464位点CC型和CT型在病例组和对照组的基因频率分别为90.15%,9.85% 和71.30%,28.70%,2组间基因型与等位基因型构成存在差异 (〖XC五号.EPS;P〗=14.105;〖XC五号.EPS;P〗=12.681,均P＜0.05)。(3)GMDR法分析结果显示,NRAMP1rs3948464和NRAMP1rs17235409位点之间存在交互作用(P＜0.05)。结论 NRAMP1rs17235409,NRAMP1rs17235416和Sp110rs3948464位点基因多态性与蒙古族结核病易患有关,NRAMP1rs17235409,NRAMP1rs17235416两位点基因多态性存在交互作用。     

Polymorphisms in sodium taurocholate cotransporting polypeptide are not associated with hepatitis B virus clearance in Chinese Tibetans and Uygurs

An association between polymorphisms in the sodium taurocholate cotransporting polypeptide (NTCP) and the natural course of hepatitis B virus (HBV) infection in the Chinese Han population has been noted. However, it is not known whether these polymorphisms are associated with the risk of developing chronic HBV infection in other racial or ethnic populations. Accordingly, we conducted a candidate single nucleotide polymorphism (SNP) association study in Tibetan and Uygur HBV-infected patients. A total of 1302 subjects including 871 Tibetans and 431 Uygurs were recruited. According to their serological and clinical characteristics, each ethnic group was divided into two groups comprising spontaneous clearance individuals and persistently infected patients. Three SNPs were genotyped by a high resolution melting curve methodology. Among the SNPs, rs2296651 exhibited a minor allele frequency of < 0.01. The frequency of allele A at rs4646287 was much higher in Tibetans (9.4% for Tibetans and 4.6% for Uygurs, p < 0.001) than in Uygurs, but the frequency of allele A at rs7154439 was the opposite (15.7% for Tibetans and 20.5% for Uygurs, p = 0.002). Irrespective of race, no significant differences in the frequency distributions of the three SNP alleles or genotypes were observed between the case and clearance groups. Moreover, none of the NTCP haplotypes were statistically different between the two groups. Data from the Tibetan patients could be grouped by HBeAg status, viral load and HBV genotype; however, no significant differences were found in the SNP genotype distribution for each characteristic. In conclusion, the NTCP polymorphisms we identified tended to be ethnicity-dependent. For Tibetans and Uygurs, no association of the three SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with HBV chronicity was observed. Examination of SNPs in NTCP for their specific associations with the course of HBV infection in other ethnic minority groups is now required.     

Factors associated with mortality in HIV-infected and uninfected patients with pulmonary tuberculosis

Background  

HIV has fuelled the TB epidemic in sub-Saharan Africa. Mortality in patients co-infected with TB and HIV is high. Managing factors influencing mortality in TB patients might help reducing it. This study investigates factors associated with mortality including patients' HIV sero-status, CD4 cell count, laboratory, nutritional and demographic characteristics in AFB smear positive pulmonary TB patients.     

张家港市肺结核相关因素研究

目的探讨影响张家港市肺结核的相关因素。方法采用非匹配设计的病例对照研究,选取2009年1月~2011年12月苏州市张家港地区新发肺结核患者为病例组,对照组是从同期健康体检人群中抽取的一个随机样本。制订统一的调查表进行面对面调查,用SPSS 19.0软件进行统计分析。结果单因素X~2检验分析结果显示性别、年龄、体重指数、文化程度、职业、接种卡介苗史、家庭有肺结核患者、流动人口等因素在病例组和对照组间之间的差异有统计学意义(均有P<0.05);多因素分析调整后显示,男性、超重或肥胖、接种卡介苗、家庭有肺结核患者、流动人口与肺结核发病相关(均有P<0.05)。其中,与文盲组相比,文化程度在小学组、初中组、高中或中专组和大专大学组发生肺结核的危险的OR(95%CI)分别是0.703(0.363,1.362)、0.405(0.214,0.767)、0.173(0.087,0.344)和0.169(0.079,0.366),呈现随文化水平提高,发生肺结核的危险性而下降的趋势(X~2=56.46,P<0.001)。结论接种卡介苗、文化水平高、超重或肥胖是肺结核的保护因素;男性、家庭...     

Congenital pulmonary tuberculosis associated with maternal cerebral tuberculosis--Florida, 2002

In 2002, congenital tuberculosis (TB), a rare disease with nonspecific signs and symptoms, was diagnosed in an infant in Florida. If untreated, congenital TB is fatal, which underscores the importance of suspecting congenital TB in newborns and infants who are at risk and who have unexplained febrile illnesses. This report summarizes the investigation of the case in Florida. Health-care practitioners should administer a tuberculin skin test to women who have risks for Mycobacterium tuberculosis infection and treat those who have latent TB infection (LTBI) to prevent maternal and congenital TB disease.     

甘肃省卫生Ⅷ支持性项目涂阴肺结核病干预试点体会

涂阴肺结核病人是潜在的传染源，对病人和社会都构成威胁。由英国政府赠款支持卫生Ⅷ项目(H8SP)在我省康乐、岷县、宕昌对涂阴活动性肺结核的发现、治疗和管理进行了为期三年半的试点活动(2001．1-2003．6在实施卫生X项目后停止)，覆盖人口90多万人，共发现病人1421例，完成治疗1389例，取得了显著成效。     

Poor performance status is associated with early death in patients with pulmonary tuberculosis

The objective of this study was to determine whether poor performance status at the start of anti-tuberculous (anti-TB) treatment is associated with early death in patients admitted to hospital with pulmonary tuberculosis (PTB). During 3 months in 2001, all adult patients admitted to eight hospitals in Limpopo Province, South Africa, and diagnosed with PTB were eligible for inclusion. At initiation of anti-TB treatment, a performance status between 0 and 4 was estimated for each patient using a modified version of the Eastern Cooperative Oncology Group scoring system. Hospital records and local TB registers were reviewed to identify patients who had died during the first 2 months of treatment. In addition, it was ascertained whether a death notification had been received by the provincial administration. Fifty-three of 295 (18%) patients died within 2 months. Mortality increased from 6% in patients with the best performance status to 51% in patients with the poorest performance status. Univariate and multivariate Cox regression analysis showed that the hazard ratio for dying was significantly higher for patients with a performance status of 3 or 4. Poor performance status shows a strong association with early death in patients with PTB and has the potential to be a useful clinical, epidemiological and research tool.     

Plasma bile acids are not associated with energy metabolism in humans

Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.     

Particles, and not gases, are associated with the risk of death in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We aim to assess the independent association of particles, after controlling for gaseous pollutants, with the risk of death among a cohort of patients with chronic obstructive pulmonary disease (COPD). METHODS: Residents of Barcelona, aged over 35 years, who attended emergency room services for COPD exacerbation from 1985 to 1989 and who died in the period 1990-1995 (n = 2305) were selected. The analysis followed a case-crossover procedure with ambidirectional controls. Air pollution exposure (particulate matter <10 microm (PM(10)), ozone, nitrogen dioxide and carbon monoxide) was measured at the city monitoring stations. RESULTS: Levels of PM(10) (odds ratio for the interquartile difference = 1.11, 95% CI : 1.00- 1.24), but not gaseous pollutants, were associated with mortality for all causes of death after adjusting for meteorological variables and influenza epidemics. In the two-pollutant models, the association of mortality with PM(10) was not confounded by the inclusion of gases, while the association of gaseous pollutants was notably reduced after adjustment for particles. There was no interaction between particles and gaseous pollutants. CONCLUSIONS: Findings reinforce the deleterious role of urban particles as a trigger of death in COPD patients, and suggest that they are the major culprit among the air pollutants. The role of other pollutants, if any, was additive and not multiplicative.     

Plasma adiponectin levels are not associated with fat oxidation in humans

OBJECTIVE: To test the hypothesis that low adiponectin is associated with low fat oxidation in humans. RESEARCH METHODS AND PROCEDURES: We measured plasma adiponectin concentrations in 75 healthy, nondiabetic Pima Indians (age, 28 +/- 7 years; 55 men and 20 women; body fat, 29.7 +/- 7.5%) and 18 whites [(age, 33 +/- 8 years; 14 men and 4 women; body fat, 28.2 +/- 10.8% (means +/- SD)] whose body composition was measured by DXA and 24-hour energy expenditure (24-hour EE) by a respiratory chamber. Respiratory quotient (an estimate of whole-body carbohydrate/lipid oxidation rate) was calculated over 24 hours (24-hour RQ). RESULTS: Before correlational analyses, waist-to-thigh ratio (WTR) and percentage of body fat (PFAT) were adjusted for age, sex, and race; 24-hour EE was adjusted for fat mass and fat-free mass, and 24-hour RQ were adjusted for energy balance. Plasma adiponectin concentrations were negatively correlated with WTR (r = -0.42, p < 0.0001) and PFAT (r = -0.46, p < 0.0001). There was no correlation between plasma adiponectin concentrations and 24-hour RQ, (r = 0.09, p = 0.36) before or after adjustment for PFAT (r = 0.001, p = 0.99, respectively, partial correlation), and no correlation was found between plasma adiponectin concentrations and 24-hour EE (r = -0.12, p = 0.27). DISCUSSION: Our cross-sectional data do not suggest physiological concentrations of fasting plasma adiponectin play a role in the regulation of whole-body fat oxidation or energy expenditure in resting conditions. Whether administration of adiponectin to individuals with low levels of this hormone will increase their fat oxidation rates/energy expenditure remains to be established.     

Energy and fat intake are not associated with abdominal adiposity

Background and objectiveCentral or abdominal obesity (AA) is a highly prevalent determinant of the metabolic syndrome and its control requires intervention strategies. This study investigated the risk factors associated with the presence of AA in hospitalized individuals.Patients and methodsA total of 1626 patients were studied. The investigated risk factors possibly associated with AA were gender, age, body mass index (BMI), habitual energy intake (HEI) and fat intake (FI). AA was determined by waist circumference (WC) and waist-to-hip ratio (WHR). The chi², Mann-Whitney and Kruskal-Wallis tests were used to compare the data and univariate and multiple logistic regressions were used to identify the predictive factors of AA.ResultsWomen were at higher risk of developing AA than men (P < 0.0001). The HEI and FI of individuals with and without AA and of women and men were not significantly different. According to multivariate analysis, HEI was not a predictive factor of AA, contrary to gender and age. The risk factors for AA, determined by WC, were gender (OR = 6.8; CI = 5.3–8.7) and age (OR = 1.0; CI = 1.0–1.0). Women were six times more likely to develop AA than men.ConclusionsEvidence of an association between AA and HEI or FI was not found, but gender and age were associated with AA.     

肺结核病新患者发现延误及影响因素分析

目的 了解浙江省新发肺结核患者发现延误的影响因素,为肺结核的早期控制提供科学依据。方法 采用回顾性研究方法收集浙江省2009年1月1日-12月31日确诊登记的31 287例新发肺结核患者病案资料,分析患者发现延误的影响因素。结果 浙江省新发肺结核患者就诊延误、诊断延误和发现延误时间中位数分别为17、1和21 d,就诊延误、诊断延误和发现延误率分别为55.66%、7.06%和62.91%;多因素logistic回归分析结果表明,羁押人群、发现地区地形为山地/岛屿、涂阳和重症患者是浙江省新发肺结核患者发现延误的危险因素;男性、15~59岁、学生/儿童、教师/医务人员/职员、服务行业人员、其他职业人员、省外流动户籍、患者来源为健康检查/转诊/追踪、发现地区地形为盆地/丘陵、诊治单位为定点医院是浙江省新发肺结核患者发现延误的保护因素。结论 新发肺结核患者就诊延误时间明显较诊断延误长;性别、年龄、职业、户籍、是否羁押人群、患者来源、发现地区地形、诊治单位类型、诊断结果、是否重症是浙江省新发肺结核患者发现延误的影响因素。     

Improved program activities are associated with decreasing tuberculosis incidence in the United States

OBJECTIVE: This study was conducted to determine whether improvements in tuberculosis (TB) program activities correlate with incident TB cases. MMETHODS: National TB surveillance data and program data from patients with pulmonary and laryngeal TB and their contacts were collected. These data were analyzed using regression models to assess the association between changes in incident TB cases and indicators of program performance (a time series of percent changes in program indices). RRESULTS: A total of 1,361,113 contacts exposed to 150,668 TB patients were identified through contact investigations. From 1987 to 1992 (the period of TB resurgence and antedating increased funding), there was a decline in several measures used by TB programs for outcomes of contact investigations. From 1993 to 1998 (the period after increases in TB funds), there was an observable improvement in the program indices. Four program indices for contacts and two for TB cases (directly observed therapy and completion of therapy) were statistically associated (p < or = .01) with the decline in TB incident cases. CONCLUSIONS: These analyses suggest that expanded TB program activities resulted in the reduction in national TB cases and underscore the importance of treatment completion for TB disease and latent TB infection. Based on these results, we propose that further improvements in these activities will accelerate the decline of TB in the United States.     

Single-nucleotide polymorphisms in Toll-like receptor genes are associated with the prognosis of gastric cancer and are not associated with Helicobacter pylori infection

Toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori (H. pylori) and initiate the innate immune response to infection. Genetic polymorphisms of TLRs play important roles in gastric carcinogenesis. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) in TLR genes and H. pylori infection in the prognosis of gastric cancer (GC). A total of 756 GC patients were included in this study. Nine SNPs (TLR2: rs3804100, rs7696323, and rs10116253; TLR4: rs10983755, rs11536878, rs1927914, and rs7873784; TLR5: rs5744174; and TLR9: rs187084) in TLR genes were genotyped by MassARRAY assay. Kaplan-Meier survival curves and Cox regression were employed to conduct the associations between SNPs in TLRs and the survival of GC. Multivariate Cox regression indicated that patients with the TLR2 rs3804100 TT genotype exhibited worse survival than those with the CC + CT genotype (HR = 1.262, 95% CI: 1.006–1.582). No significant interaction between rs3804100 and H. pylori infection was observed for the prognosis of GC. Our results suggested that the TLR2 rs3804100 polymorphism may be a potential prognostic biomarker for GC independent of the H. pylori infection-related pathway.     

SP110 gene polymorphisms and tuberculosis susceptibility: A systematic review and meta-analysis based on 10 624 subjects

Tuberculosis (TB), caused by infection of Mycobacterium tuberculosis, is a major challenge to global public health. The SP110 (Speckled 110) gene, which is considered as a host genetic susceptibility to TB, has been widely studied in recent years, yet the results were somewhat contradictory and indeterminate. We systematically searched published literatures on SP110 polymorphisms and tuberculosis risk until January 2012 in relevant databases, selected studies by previously defined criteria, extracted key data and quantitatively summarized associations of the most extensively studied polymorphisms through meta-analysis. A total of 10 624 subjects from seven case-control studies were included in the present study. In overall meta-analysis, pooled odds ratio of polymorphisms rs1135791, rs9061, rs11556887, rs3948464, rs1346311 were 1.01 (95% CI: 0.71–1.44), 0.86 (95% CI: 0.70–1.04), 0.99 (95% CI: 0.67–1.47), 1.29 (CI: 0.89–1.89) and 0.95 (CI: 0.86–1.04) respectively; the summary odds ratio of sensitivity analysis specifically on pulmonary TB were 1.02 (95% CI: 0.65–1.54) for rs1135791, 0.84 (95% CI: 0.68–1.02) for rs9061, 0.88 (95% CI: 0.57–1.36) for rs11556887, 0.94 (95% CI: 0.85–1.04) for rs1346311; and in the ethnicity stratified analysis, the estimated odds ratio were 0.97 (95% CI: 0.54–1.73) for rs1135791 and 0.86 (95% CI: 0.70–1.04) for rs9061 among Asians. None of the target polymorphisms in SP110 gene observed in the present quantitative synthesis was detected to be significantly associated with TB susceptibility. Given the moderate strength of the results, the complexities of pulmonary and extra-pulmonary host genetic polymorphisms, gene-gene and gene-environment interactions, and the cross-species difference between human and mice, it would not be robust to remark that SP110 has no role in TB progress.