青少年支气管哮喘与气道反应性的遗传流行病学分析

利用遗传流行病学的方法，调查了230个子女为青少年（6－16岁）的哮喘核心家系，分析了父或母对子女患哮喘和气道高反应性的影响。结果显示：在哮喘核心家系中，儿子比女儿更易患哮回与气道高反应性；与父母均无哮喘史家系的子女比较，父母亲的哮喘史将使子女患哮喘的危险性增加10-30倍（P＜0．01），其中母亲对子女的影响更为明显，是父亲对子女影响的两倍。父母的气道高反应性也显著增加子女气道高反应性的危险性（OR=2.49，P＜0．01）。不仅遗传因素是支气管哮喘的重要危险因素之一，而且气道高反应性与遗传因素密切相关。两者可能既有共同的遗传基础又有各自不同的遗传易感基因。     

16岁以下青少年支气管哮喘的危险因素分析

收集了仅有１６岁以下青少年为子女的支气管哮喘核心家系的资料。２３０个家系资料的分析结果表明：１６岁以下的青少年中，男性患哮喘的危险性是女性的１．６２倍（Ｐ＜０．０１），饮用塘河水的人产生哮喘的危险性明显比饮用自来水的人高（ＯＲ＝１．６７，Ｐ＜０．０５）。父母的哮喘史是青少年最为突出的危险因素，使青少年患哮喘的危险性分别增加２．０６和２．７３倍，且均具有高度显著性意义。此家系分析也显示，母亲的哮喘史对子女产生哮喘的影响更大，约为父亲的两倍。青少年自身的气道高反应性和过敏体质也是青少年产生哮喘的危险因素之一，优势比分别为１．９２和２．０１（Ｐ＜０．０１）。本文揭示了遗传因素在哮喘发病过程中可能的重要作用。     

气道高反应性对青少年支气管哮喘的影响

目的：探讨气道高反应性在青少年哮喘发病过程中的作用。方法：利用遗传流行病学的方法,收集了支气管哮喘核心家系的资料,对家系中每一成员测定其气道反应性。结果：气道高反应性的亲属患哮喘的危险性明显增加,是没有气道高反应性亲属的8．10倍（P＜0．01）;其中气道高反应性的双亲和子女患哮喘的危险性分别增加7．10倍和4．59倍,有高度显著性意义;即使调整了遗传因素可能的混杂作用,气道高反应性子女患哮喘的危险性仍较无气道高反应性子女增加2．96倍（P＜0．01）。结论：气道高反应性不仅是支气管哮喘的重要特征,而且可能是支气管哮喘的重要危险因素。     

哮喘患者气道反应性的流行病学分析

６４１个哮喘核心家系的资料分析结果显示，利用乙酰甲胆碱（ＭＴＣＨ）激发试验测定的气道高反应性，做为哮喘诊断标准的灵敏度和特异度分别是７２％、７０％。气道反应阳性者患哮喘的危险性是气道反应阴性者的５．０１倍，其中，男女患哮喘的危险性分别是４．９７倍和５．０６倍，都具有高度显著性意义。患哮喘的危险性随着气道反应性的增强而增大。同一ＭＴＣＨ剂量激发的气道反应阳性者，患哮喘的危险性随着年龄的增加而增加，且有明显的线性趋势（Ｐ＜０．０１）。无论是临床还是预防医学，气道反应性的测定都具有重要意义     

肺癌患者亲属对癌症有易感性的研究

分析了３７０例肺癌先证者的核心家系和３７０个对照的核心家系资料，发现肺癌先证者的亲属（父母、同胞）患癌症的危险性明显高于对照的亲属（父母、同胞），前乾是后者的２．０７倍（Ｐ〈０．０１）。其中患癌的危险性是对照亲属的１．８５倍，患其它癌症的危险性是３．７８倍，差别均具有高度显著性统计学意义，表明了宣威肺癌患者的亲属不仅对肺癌的易感性增高，而且对其它癌症的易感性也较高。这些结果都支持了肺癌患者的家系亲属对癌症具有遗传易感性的假设。     

慢性阻塞性肺部疾病的家族聚集性分析

为了判断慢性阻塞性肺部疾病（ＣＯＰＤ）的家族聚集性，探讨遗传因素对ＣＯＰＤ发病的影响，分析了２０６对核心家系的资料。结果表明：ＣＯＰＤ的发病具有家族聚集性。ＣＯＰＤ先证者的亲属（父母、兄弟姐妹）患ＣＯＰＤ的危险性增加，是对照家系亲属（父母、兄弟姐妹）的２．０７倍。除母亲之外，两家系父亲间，兄弟间及姐妹间患ＣＯＰＤ危险性的差异均具有显著性。故ＣＯＰＤ先证者的亲属对ＣＯＰＤ的易感性比对照的亲属高，说明遗传因素是ＣＯＰＤ的危险因素之一。     

女性肺癌的遗传流行病学研究

通过对１７６个女性肺癌先证者核心家系和１９４个女性对照的核心家系资料分析。发现女性肺癌先证者的一级亲属（父母、同胞）患肺癌的危险性是对照一级亲属（父母、同胞）的１．６７倍，且差异具有显著性。其中女性亲属患肺癌的危险性显著高于对照的女性亲属，ＯＲ值为２．８１（Ｐ＜０．０１）。女性肺癌的遗传度为２０．５４％，遗传因素是女性肺癌的重要危险因素。女性肺癌先证者的女性亲属对肺癌的遗传易感性比男性亲属高。这些结果有助于全面阐明云南省宣威县女性肺癌高发的原因。     

肺癌患者亲属对癌症具有易感性的研究

分析了３７０例肺癌先证者的核心家系和３０个对照的核心家系资料，发现肺癌先证者的亲属（父母，同胞）患癌症的危险性明显高于对照的亲属（父母，同胞）前者是后者的２．０７倍（Ｐ〈０．０１）。其中患肺癌的危险性是亲属的１．８５倍，患其它癌症的危险性是３．７８倍，差别均具有高度显著性统计学意义，表明了宣城威肺癌患者的亲属不仅对肺癌的易感性增高，而且对其它癌症的易感性也较高，这些结果都支持了肺癌患者的家系亲属对     

男性肺癌的遗传流行病学研究

为深入研究宣威县男性肺癌的病因，探讨遗传因素的作用，分析了１９４例男性肺癌先证者的核心家系和１７６例男性对照的核心家系资料。结果发现，肺癌先证者的亲属（父母、同胞）患肺癌的危险性是对照组的１．７８倍，且差异有显著性。其中，父母及女性亲属患肺癌的危险性分别是对照组的２．９０倍和２．４３倍，差异均有显著性意义。肺癌的遗传度为２４．６８％。女性对肺癌的遗传易患性比男性高，遗传因素是肺癌的重要危险因素。     

Ⅱ型糖尿病家族聚集性的流行病学研究

目的　探讨家族遗传因素在Ⅱ型糖尿病发生发展中的作用。方法　采用遗传流行病学病例对照研究方法，对常州市３５０ 个家系（１８４ 个Ⅱ型糖尿病先证家系和１６６ 个对照家系） 进行了Ⅱ型糖尿病的遗传流行病学研究。结果　病例组一级亲属总的患病率为３．４７ ％ ，与对照组的１ ．０３ ％ 相比，差异有非常显著性（χ２ ＝ １７ ．６６ ，Ｐ＜ ０ ．０１） ；无论其父母、同胞或子女，均以病例亲属的患病率显著高于对照； Ⅱ型糖尿病家族中实际发病数超过其二项分布的理论概率范围，即Ⅱ型糖尿病的分布呈明显的家族聚集性； 单因素和多因素ｌｏｇｉｓｔｉｃ 回归模型拟合也提示，家族史仍是Ⅱ型糖尿病的最主要危险因素。结论　遗传因素在Ⅱ型糖尿病发病中占有重要地位     

Genetic background of rheumatoid arthritis in connection with a family tree

Authors present a rare history of a family with accumulation of autoimmune diseases. From eight siblings four had rheumatoid arthritis, one systemic lupus erythematodes, one primary Sj?gren syndrome, and one Reiter disease. Interestingly, neither the parents nor the offsprings were affected. Because of the possible genetic background, the authors performed HLA serologic and DNA investigations in nine members of the family. The results showed, in agreement with data from the literature, the accumulation of HLA-DQ7 (DQB1*0301), DR4, B27 and DR6 (DR13) risk factors. This observation confirms, that the clinical and immunogenetic features are different in familiar and sporadic forms of rheumatoid arthritis. Authors summarize the genetic background of rheumatoid arthritis in connection with this family tree.     

成人过敏性哮喘危险因素的病例对照研究

目的 探讨导致成人过敏性哮喘及其发作的危险因素。方法 采用病例对照流行病学研究方法,收集102例成人过敏性哮喘患者和394例健康对照人群的一般社会人口学特征、疾病健康状况、吸烟史、职业接触史、室内环境状况以及家族史等信息。结果 单因素及多因素统计分析结果均显示:成人过敏性哮喘患者职业粉尘接触率高于对照组且差异有统计学显著性(P<0.05,OR=1.78);住房类型为平房/筒子楼较多层/高层楼导致过敏性哮喘或其发作的可能性大(P<0.05,OR=3.24),哮喘患者家中床褥晾晒频率较对照组低且差异具有统计学显著性(P<0.10,OR=1.53);哮喘患者家中起居室地面使用木板比例高于对照组且差异有统计学显著性(P<0.01,OR=2.33);室内油烟污染程度哮喘患者组高于对照组且差异有统计学显著性(P<0.01,OR=2.52);同时还发现,双亲中有慢性支气管炎(慢支)或哮喘疾病史可增加其子女患过敏性哮喘的危险性(P<0.01,OR=2.32)。结论 室内环境因素中住房状况差、床褥晾晒频率少、起居室地面使用木板、室内油烟污染可能是成人过敏性哮喘的危险因素,同时职业接触粉尘、双亲有慢支或哮喘疾病史也与该疾病具有一定的关系。研究结果提示成人过敏性哮喘是遗传和环境双重因素共同作用导致的一种复杂疾病。     

Familial history,age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees

The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance.     

孕母叶酸摄入与MTHFR基因C677T多态性对子代先天性心脏病发病风险研究

目的 分析孕母孕早期环境高危因素,探讨叶酸摄入与MTHFR基因多态性间交互作用对子代先天性心脏病(简称先心病)发病的影响.方法 通过病例对照研究回顾性分析98例12岁以下先心病患者母亲和101例正常婴儿的母亲(对照组)孕期危险因素暴露水平以及叶酸摄入情况,进一步应用变性液相高效色谱(DHPLC)检测MTHFR基因C677T多态性,并分析其与叶酸摄入的交互作用.结果 经Logistic回归分析,6项因素纳入先心病风险模型,孕母教育程度、没有定期产检、精神紧张、接触化学物质是子代先心病的高危因素,服用叶酸和复合维生素是先心病的保护因素.叶酸补充充足情况下,MTHFR基因各基因型比较,病例组与对照组无统计学差异.将间断服用及未服用叶酸者合并作为叶酸补充不足者,其孕母基因型为CT与CC时发病无统计学意义(P=0.066,OR=2.018,95%CI:0.95～4.285).结论 提高孕母的自我保健意识是减少先心病危险因素暴露的重要措施.怀孕早期孕母叶酸的补充不足可能是导致子代先心病发病风险增高的独立因素,孕母MTHFR基因C677T基因型合并叶酸补充不足可能增加先心病风险.

Abstract：

Objective To explore the environmental risk factors,periconceptional folate intake and methylenetetrahydrofolate reduetase (MTHFR)gene C667T polymorphism of pregnant women on congenital heart diseases (CHD)in offspring.Methods Retrospective case-control study was carried out to investigate periconceptional folate supplementation and environmental factors in 98 parents with CHD offsprings and 101 parents with normal offsprings.The mothers'MTHFR gene C667T mutation was also identified.The possible risk factors were analyzed by simple and multiple factors Logistic regression methods.Results Six factors were related to the occurrence of CHD in the offspring:education of gestation mother,no prenatal examination,under depressed or nervous condition during pregnancy and maternal exposures to harmful substance;periconceptional folate and compound vitamin supplementation were protection factors.There were significant difference between case and control group in folate supplement(P<0.05).The maternal MTHFR 677genotypes CC and TT in combination with daily folate supplements were associated with no increased risk for CHD in offspring,however in combination with not use of folate a two-fold(P=0.066,OR=2.018,95%CI 0.95-4.285)increased risk.Conclusion Improving self health care of gestational mother is the most important protection measures to avoid the risk factors exposure.Periconceptional folate deficiency may be the independence risk factor for CHD.Periconceptional mother carrying MTHER heterozygote's(CT)genotype in combination with deficiency may increase risk for CHD.     

长沙地区哮喘儿童高危因素调查

目的调查长沙地区不同年龄哮喘儿童的高危因素和各年龄层主要高危因素,为长沙地区儿童哮喘的防治和管理提供流行病学依据。方法应用湖南省哮喘防治协作组制定的哮喘儿童调查问卷,据整群抽样结果,对长沙地区0～14岁600名儿童,分婴幼儿组、学龄前组、学龄组三个年龄阶段分别进行问卷调查。在家长知情同意后,发放调查问卷,由家长与儿童共同完成调查问卷。由课题组成员收回,采用SPSS15.0统计学软件包进行统计。采用χ2检验,P<0.05为差异有统计学意义。结果通过问卷调查发现呼吸道感染是诱发各个年龄段哮喘发作的主要危险因素;婴幼儿组儿童受居住房间潮湿、天气变化、居住在主干道边等外界环境因素的影响较大(χ2=12.82,14.82,22.02,P均<0.05);学龄前组和学龄组儿童与过敏性鼻炎的发生密切相关(χ2=48.16,35.62,P均<0.05)。结论诱发哮喘的高危因素中感染因素没有年龄差异性,低龄儿童更容易受环境因素的影响,高龄儿童则受宿主和特应性影响较大。     

Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma

BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha (LTA, also called TNF-beta) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. OBJECTIVES: Our goal was to investigate whether genetic variation in TNF and LTA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. METHODS: We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families consisting of asthmatics 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04-2.28], especially among children of non-smoking parents (RR = 2.06; 95% CI, 1.19-3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% CI, 1.14-4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking.     

Indoor risk factors for asthma and wheezing among Seattle school children.

Indoor risk factors for physician-diagnosed asthma and wheezing in the past 12 months without previous asthma diagnosis were assessed in a survey of parents of 5-9-year-old Seattle primary school students. Among the 925 respondents, 106 (11%) reported a physician diagnosis of asthma, 66 (7%) had wheezing without diagnosis, and 753 (82%) were asymptomatic. After adjusting for age, sex, gender, ethnicity, medical history, socioeconomic status (SES) and parental asthma status, an increased risk of physician diagnosis of asthma was associated with household water damage, the presence of one or more household tobacco smokers, and at least occasional environmental tobacco smoke (ETS) exposure. Similarly, an increased risk of wheezing in the past 12 months among children without diagnosed asthma was associated with household water damage, presence of one or more household tobacco smokers, and occasional or more frequent ETS exposure. No increased risk of either condition was associated with gas, wood, or kerosene stove use, household mold, basement water, or wall/window dampness. Similarities in the indoor risk factors patterns between diagnosed asthma and wheezing without diagnosis suggested a similar etiology of these two conditions. The slightly higher association between ETS and asthma may indicate that parents of diagnosed asthmatics were more conscious of ETS, and were more likely to prohibit household smoking by resident smokers. Future research is needed to quantify which aspects of household water damage are related to respiratory illness.