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1.
目的 探讨染色体18q11.2区域遗传变异在中国汉族人群结核病发病风险中的作用.方法 随机抽取578例肺结核病例和756例健康对照作为研究对象.采用标签单核苷酸多态性(single nucleotide polymorphism,SNP)候选策略,基于HapMap数据库选择中国汉族人群rs4331426上下游100Kbp区域标签SNPs进行Taq-Man基因分型.结果 与非洲人群相比,rs4331426遗传变异在中国人群中较罕见.无论是否调整潜在的混杂因素,所检测的标签SNPs等位基因和基因型频率在病例组和对照组中分布的差异均无统计学意义,但该区域的单倍型可能与肺结核的发病风险有关.例如,与常见单倍型AA(rs8087945-rs12456774)相比,AG和GA携带者结核病的发病风险降低,调整OR(95% CI)分别为0.34(0.28 ~0.42)和0.21(0.16 ~0.28).结论 在非洲人群中发现的结核病易感位点rs4331426未能在中国人群中得到验证,但该位点所在的染色体18q11.2区域的单倍型可能影响中国汉族人群肺结核的遗传易感性.  相似文献   

2.
Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage.Objectives: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of white Agricultural Health Study (AHS) pesticide applicators.Methods: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach.Results: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10–6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2.Conclusions: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.  相似文献   

3.
Since there have not been any studies that quantify the influence of genetic factors on gallbladder disease (GBD) in humans using information from families, we utilized pedigree data to explore the genetic control of variation in liability to GBD. Using an extension of a variance components approach, we performed genetic analyses of GBD using information from 32 low-income Mexican-American families with two slightly different general models incorporating several sex-specific GBD risk factors. After evaluating the relative magnitudes of the covariate effects from these two models, we identified a parsimonious model including only significant predictors of GBD. According to this model, heritability for GBD was high (h2 = 0.44+/-0.18), after accounting for the significant effects of age, leptin in both sexes, total cholesterol, and HDL cholesterol in males only. We have shown quantitatively that variation in GBD is under strong genetic control. However, there are two major limitations to our findings: (1) since GBD was defined by a self-reported clinical history rather than an ultrasound examination, the prevalence of GBD could have been underestimated; and (2) since our design did not allow for shared environmental effects, our estimate of heritability may have been inflated.  相似文献   

4.
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.  相似文献   

5.
Alveolar macrophages (AMs) play a prominent role in influencing the development of lung inflammation and injury. The aim of this study is to investigate the roles of AMs response-related genes TNF-alpha, iNOS, and NRAMP1 (SLC11A1) in susceptibility to silicosis and pulmonary tuberculosis (PTB), and to analyze the interaction of dust exposure and genetic susceptibility to silicosis, interactions of TNF-alpha-308 and Natural Resistance-associated Macrophage Protein 1 (NRAMP1) INT4, D543N polymorphisms to PTB. Several epidemiological designs were used: retrospective investigations on dust exposure, case-control studies of 184 silicosis cases and 111 miners occupationally exposed to silica dust, and 1:2 matched case-control studies of 61 PTB cases and 122 PTB-free miners. The miners and controls were recruited from an iron mining operation in Anhui province, China. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect single nucleotide polymorphisms. Despite the recruitment of high dust exposure among the controls, silicosis patients still had significantly higher dust exposure than controls (242.6 +/- 98.8 vs. 217.6 +/- 100.7 mg a/m(3)). The mutation of iNOS Ser608Leu is associated with protection against silicosis and against severity of silicosis in the miners. There is a 0.47-fold (95% CI: 0.28-0.79) decrease in risk of silicosis for individuals with C/T, T/T genotype compared with the wild-type homozygous (C/C) individuals after adjustment for occupational exposure, smoking, and drinking. The protection effect of the iNOS polymorphism was particularly detected in the > or = 150 mg a/m(3) exposure group (OR: 0.44, 95% CI: 0.22-0.91). However, no interaction of dust exposure with the iNOS polymorphism was observed. Furthermore, the variant NRAMP1 INT4 genotype is significantly associated with PTB in miners. No association of other polymorphisms (NRAMP1 D543N, TNF-alpha-308) and susceptibility to silicosis or PTB in Chinese miners was found. Our data showed a 3.26-fold (95% CI: 1.47-7.23) increased risk of PTB for miners carrying both the NRAMP1 D543N G/G and NRAMP1 INT4 G/C+C/C genotypes. Additionally, in miners with TNF-alpha-308 G/G genotype, the risk of PTB increased 2.38-fold if they carry the NRAMP1 INT4 G/C+C/C genotype (95% CI: 1.14-4.98). In conclusion, the C>T mutation of iNOS Ser608Leu may be an important protective factor to miners. On the other hand, the variant NRAMP1 INT4 may play a role in the development of PTB in Chinese miners. Therefore, the novel information can be used as guideline for further mechanistic investigations and for strengthening specific protection protocols for workers.  相似文献   

6.
While circadian variations in birth and perinatal mortalityrates have previously been described in the literature, thereasons behind these observed rhythms remain unclear. The principalhypothetical causes include variations in obstetric practicesand an association between the time of birth and biologicalparameters. In order to explore this issue we analysed the distributionpatterns for time and day of birth, as well as circadian variationsin maternal characteristics, obstetric practices and neonatalrisk in a population at low obstetric risk. The study populationincluded 685 low-risk pregnant women consecutively admittedat an early stage of labour to six maternity units. The resultsshowed hourly variations in the birth rate and circadian variationsin obstetric practices that might explain the hourly patternobserved for the birth rate. By contrast, the frequency of apositive neonatal risk indicator was uniform across all timecategories in this population at low obstetric risk.  相似文献   

7.
目的 探讨炎症相关基因白细胞介素17(interleukin-17,IL-17)、Toll样受体4(toll-like receptors 4,TLR4)、嘌呤受体(purinergic receptor P2X 7,P2X7)遗传多态与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)易感性的关系。方法 采用病例对照研究设计,病例组为2015年6月~2016年5月南通市第三人民医院收集的COPD确诊患者,共152例。对照组来自参加健康体检的居民,按年龄和性别与病例进行频数匹配,共201例。基因分型采用TaqMan分型技术,关联强度采用OR值及95%CI值表示。结果 采用Bonferroni校正后,IL-17基因rs2275913、rs763780;TLR4基因rs10759932、rs2737190;P2X7基因rs1718119遗传多态与COPD的易感性关联均有统计学意义(均有P<0.05)。rs2275913A等位基因(OR=0.62,95%CI:0.46~0.86,P=0.003);rs763780C等位基因(OR=1.96,95%CI:1.29~2.98,P=0.001);rs10759932C等位基因(OR=0.49,95%CI:0.34~0.73,P<0.001);rs2737190G等位基因(OR=0.51,95%CI:0.37~0.71,P<0.001)。结论 IL-17、TLR4、P2X7基因多态影响COPD遗传易感性。  相似文献   

8.
Evidence suggests a role for progesterone in ovarian cancer development. Progesterone exerts its effect on target cells by interacting with its receptor. Thus, genetic variations that may cause alterations in the biologic functions of the progesterone receptor can potentially contribute to individual susceptibility to ovarian cancer. Using a population-based, case-control study, the authors genotyped four polymorphisms in the progesterone receptor gene (+44C/T, +331G/A, G393G, V660L) and inferred haplotypes in 987 ovarian cancer cases and 1,034 controls living in New Hampshire and eastern Massachusetts (May 1992-November 2002). Odds ratios and 95% confidence intervals were calculated to evaluate associations with ovarian cancer. No associations were observed between the +44C/T, +331G/A, and G393G polymorphisms and ovarian cancer. However, an inverse association was observed between the V660L variant and ovarian cancer (odds ratio = 0.70, 95% confidence interval: 0.57, 0.85). Associations remained after adjustment for potential confounders. Five haplotypes occurred with greater than 5% frequency, and the haplotype carrying the V660L variant had a significant association with ovarian cancer (odds ratio = 0.76, 95% confidence interval: 0.62, 0.92). Associations were similar after stratifying by ovarian cancer histologies and risk factors.  相似文献   

9.
上海市外来人员肺结核病分布与临床特征   总被引:9,自引:3,他引:6  
目的:了解上海市外来人口中肺结核病人的分布和临床特征。方法:对1996年1~12月全市外来人口活动性肺结核病报告登记资料进行分析。结果:外来人员肺结核病人总数达2279人,青壮年占总病例65%以上;男性病例为主;主要来源于江苏、浙江、安徽、四川、江西等省;登记病人来沪暂居地主要集中在市区及城乡地区,外来人口结核病管理重点在市区及城乡地区。病人分型以Ⅲ型为主。查痰率仅60.1%,但排菌率高达40%。外来人。的病例发现工作及治疗管理难度较大,目前登记病例规则化疗仅占10.4%。结论:有必要通过有关部门的共同协作,拟定切实可行的外来人口结核病管理办法。  相似文献   

10.
11.
Racial variation, twin studies, segregation analyses, linkage and association studies all suggest that genetic factors play an important role in predisposition to tuberculosis. Many previous studies have been performed with pulmonary TB patients, as the most prevalent form of clinical TB (nearly 95%), and very few of them have considered extrapulmonary TB. The present study evaluates the effects of variation in eight candidate genes (LTA, TNF, IL1B, IL1RN, IL10, TGFB1, TIRAP and P2X7) with pulmonary, pleural, miliary and other extrapulmonary forms of TB in a Peruvian population from the North of Lima. 626 TB cases and 513 healthy controls were enrolled in this study. LTA+368 and IL10?592 were associated with different clinical forms of TB (P < 0.05). LTA+368 genotype A/A was protective for pleural TB, LTA+368 G/A was correlated with susceptibility to miliary TB. Genotypes A/A and G/A were associated with protection and susceptibility respectively when considering all extrapulmonary TB forms versus either healthy controls or pulmonary TB patients. Carriers of IL10?592*C were under-represented among those with pulmonary TB and all TB forms (P < 0.001). IL10?1082IL10?592 haplotypes showed different distributions among patients with pulmonary TB and all TB forms (P < 0.01) when compared to healthy controls. In addition, IL10?1082IL10?592 haplotypes showed differences between pleural, miliary and all forms of extrapulmonary TB when compared with pulmonary TB (P < 0.05). All findings are consistent with an under-representation of the IL10?1082*A–IL10?592*A haplotype in pulmonary TB patients. These results suggest that the polymorphisms LTA+368 and IL10?592, or variants in strong linkage disequilibrium, variably affect susceptibility to the differing clinical forms of TB in Peruvians.  相似文献   

12.
Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to cancer risk. However, epidemiologic findings have been inconsistent. The authors conducted meta-analyses of associations between genes in the base excision repair pathway and cancer risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1). They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity. They found a protective effect of the XRCC1 194Trp allele for tobacco-related cancers (OR = 0.86, 95% CI: 0.77, 0.95), using 4,895 cases and 5,977 controls from 16 studies; this is compatible with evidence of lower mutagen sensitivity for this allele. The XRCC1 399Gln/399Gln genotype was associated with increased risk of tobacco-related cancers among light smokers (OR = 1.38, 95% CI: 0.99, 1.94) but decreased risk among heavy smokers (OR = 0.71, 95% CI: 0.51, 0.99), suggesting effect modification by tobacco smoking. There was no association between cancer risk and the APE1/APEX1 Asp148Glu and XRCC1 Arg280His polymorphisms. Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure.  相似文献   

13.
Spoligotyping was performed on 540 Mycobacterium tuberculosis isolates in order to evaluate the genetic biodiversity of tubercle bacilli in India. One hundred and forty seven patterns were unique and 393 were grouped in 48 clusters. Comparison with an international spoligotype database showed that the most predominant clades among tuberculosis (TB) isolates were Central Asian (CAS) and East-African Indian (EAI) with shared-types (ST) ST26 and ST11 alone being responsible for 34% of all TB cases. Twenty one (3.8%) isolates belonged to the Beijing genotype. Marked variations were observed among circulating strains, STs belonging to CAS family predominated in the North, whereas the EAI family was more common in the Southern India. TB in India is predominantly caused by strains belonging to the principal genetic group 1 (PGG1), suggesting that most of the TB burden in India may be traced to ancestral clones of the tubercle bacilli. This study gives an insight into the global M. tuberculosis genetic biodiversity in India, the predominant spoligotypes and their impact on disease transmission.  相似文献   

14.
Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50-70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C677T single-nucleotide polymorphism (SNP) in the methylenetetrahydrofolate reductase (MTHFR) gene, and the observation that elevated plasma homocysteine levels are associated with NTD, research has focused on genetic variation in genes encoding for enzymes of folate metabolism and the closely-related homocysteine metabolism. In the present review relevant SNP in genes that code for enzymes involved in folate transport and uptake, the folate cycles and homocysteine metabolism are summarised and the importance of these SNP discussed in relation to NTD risk.  相似文献   

15.
This paper presents the first evaluation of the molecular epidemiology of Mycobacterium tuberculosis in Peru. We characterised 323 isolates using spoligotyping and mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTR) typing. We aimed to determine the levels of genetic diversity and genetic differentiation among and within Peruvian isolates and the epidemiological factors which may be driving patterns of population structure and evolution of M. tuberculosis in Peru. Our results compared to the fourth international spoligotyping database (SpolDB4) and MIRU-VNTRplus, show that the main M. tuberculosis families present are Latin American-Mediterranean, Haarlem, T, and Beijing. Bayesian clustering recovered 15 groups in the Peruvian M. tuberculosis isolates, among which two were composed mainly of orphans, implying the presence of native "Peruvian" strains not previously reported. Variable levels of association with drug resistance were observed, with Beijing genotypes not showing any association with multidrug resistance, while in other groups MIRU-VNTR loci 2, 23, 31, and 40 were found to be associated with the multidrug-resistant tuberculosis (MDR-TB) phenotype, suggesting that a linkage disequibrium between these MIRU and drug resistance loci may be present. Genetic differentiation was present among drug resistant and sensitive strains. Ethambutol appeared to be the main driver of differentiation, suggesting that strong selection pressure could have been exerted by drug treatment in Peru over recent years.  相似文献   

16.
摘要:目的 了解武汉市某女子监狱羁押人员的肺结核病疫情及治疗现状,为制定有针对性的肺结核预防控制策略和措施提供科学依据。方法 对武汉市某女子监狱的所有羁押人员进行肺结核筛查,并对患者进行治疗。结果 2 326人进行了胸部X线检查,48人完成了痰涂片和痰培养,共确诊22例活动性肺结核患者,患病率为945.83/10万,仅培阳肺结核患病率为42.99/10万。除特殊病例无法接受化疗话,其余肺结核患者均开始接受个体化方案的治疗。结论 女子监狱肺结核疫情严峻,对女性羁押人员进行定期肺结核筛查、及时治疗、加强宣教等干预是十分必要的。  相似文献   

17.
目的 了解流动人口对苏州市肺结核流行特征的影响,为制定防治对策提供科学依据。方法 收集2008-2013年苏州市肺结核病例和人口资料,分析流动人口肺结核对当地肺结核流行特征的影响。 结果 流动人口肺结核发病率高出本地人口21.6%,升高总人口发病率10.5%,使全市发病率下降速度减缓了4.4%。流动人口与总人口发病率的相关程度高于本地人口与总人口的相关程度(t=14.63,P<0.001)。流动人口对全市8/9地区的总人口发病水平的贡献率为正值,提高这些地区总人口发病率0.3%~42.3%;对<45岁人群发病贡献率为61.4%,对女性人群发病贡献率为36.0%,大幅提高了这些人群的发病水平。流动人口改变了肺结核的地区分布和病人的职业构成。 结论 流动人口肺结核对苏州市肺结核流行特征的影响已超过了本地病人,明显改变了该病在苏州市的流行特征。应采取针对性措施加强流动人口结核病防制工作。  相似文献   

18.
The introduction of chemotherapy dramatically changed the epidemiology of tuberculosis as the risk of infection was thereby nearly eliminated. The present paper illustrates the risk of disease under these conditions. A large and representative segment of the Danish population, a total of over 626 000 persons aged 15-44 years, was examined by a standardized technique in 1950-52 and has now been followed for 12 years. It has been possible by means of simple parameters such as infection and vaccination status, X-ray lesion and age to divide the population into groups with widely different incidence rates. The time trend in disease rates among vaccinated persons and natural reactors suggests that post-primary tuberculosis is of great significance in the present tuberculosis situation. Three-quarters of all cases stem from the natural reactors. It would have been of great practical significance to identify high-risk groups which yielded a great part of the patients. This was not possible since the majority of cases developed among reactors whose distinctive feature was that they were infected at time of examination.  相似文献   

19.
目的 了解谷胱甘肽转移酶M1(GSTM1)和T1(GSTT1)基因多态性在中国人群及吉林省结核涂阳人群中的分布.方法 采用系统综述方法,以"GSTM1/GSTT1+多态性"为关键词搜索国内发表于2009年1月以前、研究类型为横断面研究或队列研究基线的文献,经综合分析获得GSTM1、GSTT1基因多态性分布信息.以吉林省14个县(区)2007年11月至2008年5月间的全部结核涂阳病例(共1120名)为研究对象,采用多重PCR法检测GSTM1、GSTT1基因型.结果 系统综述得到中国人群GSTM1、GSTT1基因纯合缺失型和GSTM1-GSTT1联合缺失基因型频率分别为54.2%、46.8%和26.2%,其中以汉族为主的人群分别为53.4%、44.9%和25.5%;本研究中吉林省结核涂阳人群相应频率分别为57.2%、20.4%和13.7%,GSTM1、GSTT1基因型及组合基因型分布的性别、年龄差异无统计学意义(P>0.05).与系统综述结果相比,本研究人群GSTM1纯合缺失基因型频率偏高(P=0.016),GSTT1纯合缺失基因型和GSTM1-GSTT1联合缺失基因型频率明显偏低(P值均<0.001).结论 GSTM1、GSTT1基因多态性分布存在种族差异;本研究人群结果与系统综述结果的统计学差异可能是由于前者样本量较大、既往研究对象多为南方人群所致.  相似文献   

20.
目的 探讨慢性阻塞性肺疾病(COPD)合并肺部感染患者Toll样受体7(TLR7)多态性及血清TLR7/白细胞介素-17(IL-17)/白细胞介素-23(IL-23)水平变化。方法 选择海口市中医医院呼吸内科2018年10月-2020年10月收治的COPD合并肺部感染患者75例作为研究对象纳入研究组。选择同期医院收治的COPD未合并感染者80例纳入对照组,入组时抽取外周静脉血,采用聚合酶链式扩增反应检测TLR7基因rs3853839位点基因型分布,以测序结果确定基因分型。根据肺部感染评分对研究组患者肺部感染严重程度进行评价。结果研究组CC基因型、C等位基因频率高于对照组(P<0.05),校正性别、年龄、COPD病程、合并糖尿病、合并哮喘及合并吸烟情况等常量因素后,Logistic回归分析结果显示携带TLR7基因rs3853839位点CC基因型、C等位基因是COPD合并肺部感染的独立影响因素(P<0.05);三组患者血清TLR7、IL-17、IL-23整体水平差异具有统计学意义(P<0.05),CC型研究组患者血清TLR7、IL-17、IL-23水平高于GG和GC型(P...  相似文献   

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