Novel single nucleotide polymorphisms of the human nuclear factor kappa-B 2 gene identified by sequencing the entire gene

The nuclear factor kappa-B 2 (NFKB2) gene is a member of the NFKB/Rel gene family, which is known to be a pivotal regulator of the acute phase of the inflammatory response and of immune responses. We identified three novel single nucleotide polymorphisms (SNPs) and determined their allelic frequencies, as determined by the sequencing of 48 alleles of the entire gene in a Japanese population sample. Two of the three polymorphisms were identified at nucleotide (nt) position 1837 (T/C) and nt position, 1867 (GG/G) in the upstream region of the gene. The other polymorphism was identified at nt position 2584 (G/T) within intron 1. These polymorphisms will be useful in genetic studies of the processes involved in inflammatory responses and in bone differentiation. Received: October 17, 2000 / Accepted: October 23, 2000     

Using linked markers to infer the age of a mutation

Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a “direct” estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine‐tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine‐scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as “composite” likelihood and moment‐based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87–100, 2001. © 2001 Wiley‐Liss, Inc.     

Genetic markers in the Tuvan population of Todja, Siberia

Todja is a secluded region of northern Tuva situated in the Sayany Mountains, Siberia. The aboriginal population of Todja is Tuvan. A total of 128 healthy Tuvans living in Todja were typed for HLA-A, -B and -C antigens and several plasma and erythrocyte protein polymorphisms (Hp, Tf, Gc, ESD, ACP, PGM1, PGD and ADA). The observed frequencies of all 8 blood protein and HLA genotypes were in agreement with Hardy-Weinberg expectations. The most frequent HLA antigens in Todjans are A2 (0.36). A3 (0,24), A9 (0.50), B15 (0.34) and B40 (0.50). HLA haplotypes A2B5, A2B40, A9B15 and A9B40 are most common in this population. The observed frequencies of protein polymorphisms and HLA antigens and haplotypes in Todjans are similar to those of other Mongoloid populations. A comparison of HLA frequencies currently observed in Todjans with those obtained 20 years ago at the same locality showed minor changes attributable to the effect of migration.     

Can subjects with a positive allergen skin test be selected by a short questionnaire?

The objective was to evaluate a postal questionnaire screening procedure for selection of subjects with positive reactions to skin prick tests with common allergens. The project consisted of a screening, with subsequent skin prick test of two selected groups. The setting was the Glostrup Population Studies institute in Copenhagen, Denmark. Participants in the screening included 8000 subjects, aged 15–69 years. The subjects were randomly selected from the population of western Copenhagen County, Denmark. From the 6998 respondents (87.5%), 793 subjects were randomly selected (Random Group), and 788 subjects were chosen on the basis of their answers to the questionnaire (Symptom Group). Both groups were invited to take skin prick tests. Attendance rates were 75.5% (Random Group) and 80.6% (Symptom Group).
The main outcome measures were responses (yes or no) to the specific questions and the subjects' skin reaction (positive or negative). The association between symptoms and skin reactivity, adjusted for the effects of sex and age, was summarized by odds ratios. Symptoms on exposure to allergens were highly associated with positive skin reactivity. In the Symptom Group the percentage of subjects with at least one positive skin reaction was 57.7%, which was twice as much (28.4%) as in the Random Group. The results show that it was possible to select a group with high skin reactivity on the basis of the symptoms reported in the screening. Questions about exposure to allergens were the most appropriate for selection of this group.     

Fear of Movement/Injury in the General Population: Factor Structure and Psychometric Properties of an Adapted Version of the Tampa Scale for Kinesiophobia

In recent years, several studies have pointed out the importance of pain-related fear in the development and maintenance of chronic pain. An important instrument for measuring pain-related fear in the context of low back pain is the Tampa Scale for Kinesiophobia (TSK). Recently, a version of this questionnaire has been developed for administration among the general population (TSK-G). To determine the factor structure of the TSK-G, data from a random sample of the Dutch general population were studied separately for people who had had back complaints in the previous year, and people who had been without back complaints. For both groups the TSK-G appeared to consist of one, internally consistent, factor of 12 items. The one-factor TSK-G also appeared valid after comparison with scores on measures of catastrophizing and general health status.     

Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001     

我国消除丙型肝炎的普通人群HCV检测策略的成本效果分析

目的 分析我国消除丙型肝炎（丙肝）的普通人群HCV检测策略的成本效果,明确最佳成本效果的HCV检测年龄。方法 运用TreeAge pro 2019软件构建决策树马尔科夫模型,以1年为周期,模拟10万名20~59岁各年龄组人群HCV检测和治疗结果,以全社会角度分析策略间比较的成本效果和效益。效果指标为增量成本效果比（ICER）,效益指标为净货币效益（NMB）,以我国2022年人均国内生产总值（85 698元）为意愿支付阈值。通过单因素敏感性分析和概率敏感性分析评估结果可靠性。结果 在20~59岁人群HCV检测有成本效果,在40~49岁年龄组进行HCV检测成本效果最佳。20~59岁年龄组人群HCV检测策略与未HCV检测策略比较,增量成本为161.24元/人,增量效用为0.003 6质量调整寿命年（QALYs）/人,ICER为45 197.26元/QALY,ICER小于意愿支付阈值,具有成本效果。各年龄组人群HCV检测策略与未HCV检测策略比较,ICER为42 055.06~53 249.43元/QALY,NMB为96.52~169.86元/人,其中40~49岁年龄组的ICER最低,NMB最高。单因素敏感性分析结果显示,贴现率、丙肝抗体（抗-HCV）检测成本、人群抗-HCV阳性率和直接抗病毒药物治疗成本对经济学评价影响较大,但改变参数取值,结论不变。概率敏感性分析结果表明模型分析结果稳定。结论 医疗机构探索动员20~59岁普通人群进行HCV检测具有较好的成本效果,以40~49岁年龄组人群的HCV检测成本效果最佳。在我国普通人群中实施HCV检测的“愿检尽检”策略,能降低人群丙肝疾病负担。     

职业人群不健康行为生活方式与高尿酸血症的关系及高血压、血脂异常的效应修饰作用

目的 探索不健康行为生活方式与高尿酸血症的关系,以及高血压、血脂异常的效应修饰作用,为预防高尿酸血症提供理论依据。方法 采用横断面调查研究设计,基于2021年10-12月来自四川省、贵州省28个地级市和重庆市33个区（县）中国铁路成都局集团有限公司的西南职业人群队列基线数据,通过问卷调查、体格测量及实验室生化检测收集研究对象的人口学特征、行为生活方式、慢性非传染性疾病患病情况。不健康行为生活方式得分根据吸烟、饮酒、膳食模式、体力活动和低体重/超重状况进行评分,分值越高不健康行为生活方式越多。采用多因素logistic回归模型分析不健康行为生活方式评分、吸烟状况、饮酒状况等与高尿酸血症的关系,采用分层分析探索高血压等疾病对不健康行为生活方式与高尿酸血症之间关系的修饰效应。结果 共纳入11 748名研究对象,高尿酸血症患病率为34.4%。多因素logistic回归分析显示,现在吸/既往吸烟、现在饮/既往饮酒及BMI异常是高尿酸血症患病的危险因素,不健康行为生活方式对高尿酸血症患病风险呈现累积效应,随着得分的升高,高尿酸血症患病风险升高,OR值由1.64（95%CI：1.34~2.00）上升至2.89（95%CI：2.39~3.50）。分层分析结果显示,在高血压及血脂异常人群中,不健康行为生活方式对高尿酸血症患病风险影响更大。结论 多种不健康行为生活方式的共存会升高高尿酸血症患病风险,这一效应在高血压、血脂异常人群中更明显。及时纠正不健康行为生活方式,并控制高血压和血脂异常,降低患高尿酸血症的风险。     

Polymorphism analysis of the VNTR locus D17S5 in Central Spain

The fragment length polymorphism YNZ22 (D17S5) was analysed for a sample of 207 unrelated individuals living in Madrid (Spanish Caucasians) using PCR-methodology and high resolution separation. Hardy-Weinberg expectations (HWE) were calculated after pooling alleles into four groups. No deviations from HWE were detectable using the conventional ²-test. The power of discrimination was estimated as 0.96 and the mean paternity exclusion chance as 0.7587. A comparison of the allele frequency distribution with those of other Caucasian groups revealed no major differences.