HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs

A total of 106 pairs of identical twins, of whom 56 were concordant and 50 discordant for insulin-dependent diabetes, were typed for HLA-DR. In both the concordant and discordant groups there was a high prevalence of the antigens DR3 and DR4, a low prevalence of DR5 and DR7, and a virtual absence of DR2. The heterozygous phenotype DR3,DR4 was more prevalent in concordant than discordant pairs. This was therefore the first demonstration of a genetic difference between concordant and discordant identical twin pairs. These findings suggest that possession of both DR3 and DR4 antigens confers a greater genetic predisposition to insulin-dependent diabetes than does the possession of either antigen alone.     

Perinatal risk factors and neonatal complications in discordant twins admitted to the neonatal intensive care unit

Background Many studies have shown a relationship between birth weight discordance and adverse perinatal outcomes.This study aimed to investigate the perinatal risk factors and neonatal complications o...     

遗传和环境对于男性开始吸烟影响的双生子研究

目的：分析遗传和环境因素分别对于男性吸烟行为和开始吸烟年龄的影响。方法：回顾性调查1 006对18岁及以上成年双生子的吸烟状况及开始吸烟年龄,在分析同卵和异卵双生子同吸烟率的基础上分别计算吸烟行为和开始吸烟年龄的遗传度。结果：与西方文化不同,该双生子人群中男性吸烟比例达66.8%,相比之下女性仅有0.2%。同卵双生子中, 88.7%(566/638对)的双生子对中两个成员都是吸烟者或者具有吸烟经历或均不吸烟,而异卵双生子此比例仅为63.6%(234/368对)。该双生子样本吸烟行为的遗传度为69.0%±4.1%。双生子平均开始吸烟年龄（20.4±5.3）岁,同卵双生子开始吸烟年龄相关系数0.393,而异卵双生子达0.860。结论：中等程度的遗传度显示遗传因素对于男性双生子选择是否吸烟具有一定的影响,但是什么时候开始吸烟,更多取决于个人环境的影响。     

THE STUDY OF DENTAL CARIES AMONG 280 TWIN PAIRS

The twin study was intent a to estimate the relative influence of hereditary factors and environmental factors in causing caries. The subjects selected from the city Beijing, China, are 280 same-sexed twin pairs. 186 pairs are monozygotic (MZ) twins; the other 94 pairs are dizygotic (DZ) twins. The total sample involved in the present study was significantly great in size and different statistical methods of analysis were adopted. The conclusion reached is such that non-genetic factors rather than genetic factors have more influence in causing caries.     

Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics

Forty-eight out of 53 non-insulin-dependent diabetic identical twin pairs were concordant for diabetes. In the five discordant pairs the diabetic twin had only recently been diagnosed. Oral glucose tolerance tests were carried out on the unaffected twins of the five pairs and on matched controls. Fasting concentrations of blood glucose (5.5 +/- 0.6 v 3.7 +/- 0.3 mmol/l; 99.1 +/- 10.8 v 66.6 +/- 5.4 mg/100 ml), haemoglobin A1 (mean 9.1%, range 8.8-9.2% v mean 7.9%, range 7.4-8.4%), lactate, alanine, and glycerol (0.090 +/- 0.017 v 0.045 +/- 0.008 mmol/l); and the lactate: pyruvate ratio were significantly higher in the twins than controls. After glucose challenge blood glucose, lactate, alanine, and glycerol concentrations and lactate: pyruvate ratio were increased in the twins. Insulin response was severely impaired, being almost absent in four of the five twins. The non-diabetic members of the discordant non-insulin-dependent diabetic pairs showed noticeable metabolic abnormalities which would later presumably deteriorate to frank diabetes. These findings, taken with the high concordance rate for non-insulin-dependent diabetic twins, suggest that non-insulin-dependent diabetes is predominantly, possibly entirely, inherited.     

妇科常见病在双生子队列中的研究进展

双生子研究是分析复杂疾病中遗传与环境因素的一种经济有效的方法,在许多疾病的病因学研究中广泛应用。经典的双生子研究通过比较同卵双生子和异卵双生子的表型异同来分析疾病的遗传度。随着分子生物学的发展,双生子研究与组学的结合逐渐成为一种前沿有效的研究方法。疾病表型不一致的双生子对照研究是对传统病例对照研究的有力改进。在妇科疾病方面,西方通过双生子研究解析高加索人群中几种常见妇科病的病因特点,包括盆底疾病、子宫肌瘤、子宫内膜异位症、多囊卵巢综合征等。主要研究发现包括:在女性压力性尿失禁及盆腔器官脱垂中,环境因素的影响均高于遗传因素;遗传因素对子宫肌瘤的发病影响大于环境因素;双生子非共有环境因素对子宫内膜异位症的发生影响较大,不孕与子宫内膜异位症密切相关;遗传因素在多囊卵巢综合征的病因中有重要作用;女性性高潮障碍具有遗传基础等。而目前,尚无在亚洲人群中开展的妇科疾病双生子研究。中国双生子队列现已招募珍贵的2万余对女性双生子,有待系统收集妇科疾病信息,结合分子生物学研究方法,将对我国常见妇科病的认知有所突破,从而能更好地指导我国妇科疾病的诊治。双生子队列的扩建和长期维护将是未来面临的主要困难。      

A twin study of the effects of the Vietnam War on posttraumatic stress disorder

This study evaluates the impact of military service during the Vietnam era (1965 to 1975) on posttraumatic stress disorder using a sample of 2092 male-male, monozygotic, veteran twin pairs. Data were collected in 1987 using mail and telephone interviews. In 715 monozygotic twin pairs who were discordant for military service in southeast Asia (SEA), posttraumatic stress disorder was found to be strongly associated with military service in SEA. The prevalence of posttraumatic stress disorder was 16.8% in twins who served in SEA compared with 5.0% in co-twins who did not serve in SEA. There was a ninefold increase in the prevalence of posttraumatic stress disorder (95% confidence interval, 4.8 to 17.6), comparing twins who experienced high levels of combat with their co-twin who did not serve in SEA. Our results demonstrate that nearly 15 years following the end of the Vietnam War, there remains a substantially increased prevalence of posttraumatic stress disorder among veterans who served in SEA.     

Cantrell syndrome in one of a set of monozygotic twins

Cantrell syndrome is a rare syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium and the heart. The spectrum of anomalies varies widely. A full syndrome, probable syndrome and incomplete expression have been described. Less than 160 cases have been described in the world literature. Only one set of monozygotic twins concordant with the syndrome has been reported. To our knowledge, the syndrome affecting only one of a set of twins has not been reported. We report a premature infant, the first-born twin, with the syndrome. The omphalocoele was large, and heart abnormalities included dextrocardia with atrial septal defect. The co-twin is normal.     

妊娠早期不同一性发育双胎的妊娠结局

目的:评估双胎妊娠早期两胎儿不同一性发育的妊娠结局.方法:回顾性研究在216对双胎妊娠中共有19例(不同一组),41例为对照组.用方差分析和Fisher's exact test比较两组胎儿生长受限(IUGR)发生率、新生儿不同一性发生率和早产发生率情况.结果:不同一组IUGR发生率、新生儿不同一性发育发生率以及早产发生率分别为57.2%,35.7%,78.6%,显著高于对照组24.4%,7.5%和30%(P值分别为0.03,0.02和0.01),不同一组先天畸形的发病率高于对照组,当双胎不同一性比率(A-B/A)＞25%时,有显著性差异(P=0.039).所有发现的畸形均为易于识别的严重畸形.结论:双胎不同一性发育可发生于妊娠早期.双胎不同一性程度＞25%时,胎儿畸形率增高且为易识别的显著畸形.早期不同一性发育双胎的IUGR发生率、新生儿不同一性发生率和早产发生率均增高.     

A twin study of human obesity

Height, weight, and body mass index (BMI) were assessed in a sample of 1974 monozygotic and 2097 dizygotic male twin pairs. Concordance rates for different degrees of overweight were twice as high for monozygotic twins as for dizygotic twins. Classic twin methods estimated a high heritability for height, weight, and BMI, both at age 20 years (.80, .78, and .77, respectively) and at a 25-year follow-up (.80, .81, and .84, respectively). Height, weight, and BMI were highly correlated across time, and a path analysis suggested that the major part of that covariation was genetic. These results are similar to those of other twin studies of these measures and suggest that human fatness is under substantial genetic control.     

同卵双胞胎胆道闭锁患儿染色体核型和全外显子组测序分析

目的:以临床表型不同的同卵双胞胎胆道闭锁（BA）患儿为研究对象,分别进行染色体G显带核型分析和全外显子组测序,检测该组双胎儿是否存在染色体核型异常和差异基因型,初步探讨胆道闭锁发生的遗传学背景。方法:采集3对同卵双胞胎BA患儿外周静脉血作为实验样本,分别进行染色体G显带核型分析和全外显子组测序分析。结果:临床表型不同的同卵双胞胎BA患儿,其染色体G带核型分析结果均无异常,为46,XX或46,XY。全外显子组测序结果显示,未检测到该组同卵双胞胎BA患儿的任何差异基因型。结论:同卵双胞胎BA患儿具有不同的临床表型,其染色体G显带核型正常,提示胆道闭锁的发生与染色体异常无关;双胎儿全外显子组测序检测不存在差异基因型,提示胆道闭锁不是单纯的遗传性疾病,可能与遗传表型或外显率以及其他因素等有关。     

乙型肝炎病毒感染后表型不一致的单卵孪生子基因组CpG岛甲基化谱差异分析

目的进行乙型肝炎病毒感染后表型不一致的单卵孪生子基因组CpG岛甲基化谱差异分析,以发现可能的差异甲基化基因。方法采用改良甲基化间区位点扩增技术,根据人基因组CpG岛甲基化位点的两种主要碱基组合,-CGCG-和-CCGG-,用3种不同的酶切组合（SmaⅠ—XmaⅠ、HpaⅡ-MspⅠ、BssHⅡ—PauⅠ／BsePⅠ）,同时采用Personal Molecular Imager FX分子成像系统及放射自显影相结合的方法,经Quantity One 4．4．0凝胶图像分析软件进行差异条带分析,分离回收差异甲基化条带并克隆人T载体,阳性克隆进行测序,将测序结果进行BLAST分析,初步了解与乙型肝炎病毒感染后表型不一致的单卵孪生子相关的差异甲基化基因情况。结果在一对表型一致的单卵孪生子间基因组CpG岛甲基化分析显示条带几乎相同,而在另一对表型一致以及一对表型不一致的单卵孪生子之间均存在差异甲基化条带,前者差异甲基化条带数目少于后者,将得到的差异甲基化条带克隆人T载体,目前测序分析得到4个可能与乙型肝炎病毒感染后表型不一致的单卵孪生子相关的差异甲基化基因。结论乙型肝炎病毒感染后表型不一致的单卵孪生子间基因组CpG岛甲基化水平有差异,其对疾病表型的影响及机制尚需后续深入研究。     

Cardiac dimension changes with endurance training. Indications of a genotype dependency

We studied the sensitivity of cardiac structures to endurance training. To evaluate variability in adaptation, 20 sedentary subjects and ten pairs of monozygotic twins were submitted to a 20-week endurance training program. Maximal oxygen uptake increased significantly in both groups: 11 mL O2/kg/min-1 or 30% in the sedentary group and 6 mL O2/kg/min-1 or 13% in the monozygotic twins. Statistically significant increases in left ventricular diameter, posterior wall and septal thicknesses, as well as left ventricular end-diastolic volume and left ventricular mass were observed in the sedentary subjects, but not in the monozygotic twins. We could demonstrate that after training, twin pairs differed more from each other than at the start. Concomitantly, within-pair resemblance was greater after training than before. Results indicate that cardiac dimensions are amenable to significant modifications under controlled endurance training conditions and furthermore that the extent and variability of the response of cardiac structures to training are perhaps genotype dependent.     

Concordant childhood acute lymphoblastic leukemia in monozygotic twins

Two 4-year-old monozygotic Chinese, female twins developed concordant childhood acute lymphoblastic leukemia (ALL) within an interval of about 2 weeks. Based on morphology and cytochemistry findings of the bone marrow blast cells, a diagnosis of ALL, L1 was made. Immunophenotyping showed the blast cells of both twins expressed similar antigens, i.e. HLA-DR, CD10, CD13, CD19, CD22 and CD34. Identical blood group, same HLA (human leucocyte antigen) genotype, sex and similar appearance suggest that the twins are monozygotic. Since the bone marrow leukemic cells of both twins were identical in morphology and expressed the same antigens with almost similar percentages of positivity, it is likely that the blast cells were derived from the same single clone. Based on the single clone hypothesis, the leukemogenic event must have arisen in utero in one twin and the cells from the abnormal clone then spread to the other twin via shared placental anastomoses.     

单卵双胎儿表型不一致性共同性斜视

①目的通过分析单卵双胎儿表型不一致性共同性斜视发病因素,探讨其发病机制。②方法回顾性分析在我院就诊的表型不一致性斜视单卵双胎儿7对14例,记录出生后体质量、产期,有无家族发病史、外伤史或神经系统疾病史。检查屈光、斜视角、眼球运动等以确定斜视类型。③结果外斜视与正位视结合5对,内斜视与正位视结合2对。7对单卵双胎儿中6对早产,13例体质量低于2 500 g。斜视表型病儿体质量明显低于非斜视病儿(P=0.039 1)。7例弱视中的5例见于斜视表型,另2例见于非斜视表型。所有伴斜肌异常、分离性垂直斜视或眼球震颤者均见于斜视表型。④结论发生于单卵双胎儿的不一致性斜视揭示了环境因素在斜视发生中所起的作用。出生时低体质量、早产可能与不一致性共同性斜视的发生有关。     

双生子视网膜母细胞瘤遗传学和临床表现

报告一对经生育史,红细胞血型(ABO、MN、Rh、P),血清型(Hp,Gc),酯酶D(EsD)表型及HLA(A、B、Cw)多种遗传标记检测而确诊为同卵双生子的视网膜母细胞瘤病例,同时于45天出现“猫眼”症状,孪生弟右眼、孪生兄双眼眼球摘除后,病理检查证实为视网膜母细胞瘤(Rb),分化型。文章结合本世纪文献报道作过卵性诊断的Rb双生子共33对,计算出同卵双生患病一致率和Rb的遗传指数(76.56％);并就双生子卵别鉴定项目的可靠程度,“镜像”现象以及如何用Knudson的“二次突变”假说来解释同卵双生子发病一致性的问题,作了简要的讨论。     

人体腺苷脱氨酶活性的遗传性探讨

作者采用卵性鉴定准确性在98％以上的双生子法,对22对单卵双生子及16对双卵双生子进行腺苷脱氨酶(ADA)活性的遗传性研究。结果发现,单卵双生子对的ADA活性相关系数为0.73,双卵双生子对的ADA活性相关系数仅为0.47。说明遗传因素对血中ADA活性的大小起着一定作用,但不能忽视环境因素的影响。用四种方法计算,其遗传度为49～80％。     

芜湖市198对双生儿的调查分析

通过对芜湖市中、小学和幼儿园的58 887名学生的普查,发现198对双生子,双生子发生率为3.4‰,其中同卵双生占60.77％,异卵双生占39.23％。本文就双生子的胎次和父母育龄的分布;双生子的智力、体征;双生与遗传等方面进行了研究。     

发育不同一性双胎妊娠的妊娠结局临床分析

目的探讨发育不同一性双胎妊娠的临床诊断、处理与妊娠结局。方法以双胎胎儿体重差〉20%为发育不同一性双胎妊娠诊断标准,回顾性分析比较1997年1月-2009年8月间中山三院分娩的66例发育不同一性双胎妊娠（观察组）与同期312例发育一致双胎妊娠（对照组）的临床资料,比较两组在妊娠并发症、合并症、分娩情况和围产儿预后等的差异。结果观察组晚期流产、早产、羊水过多、双胎输血综合征、双胎之一胎死宫内和胎盘早剥的发生率分别为18.2%（12/66）、63.6%（42/66）、30.0%（20/66）、34.8%（23/66）、13.6%（9/66）和4.5%（3/66）,对照组为8.0%（25/312）、35.9%（112/312）、14.7%（46/312）、1.3%（4/312）、3.8%（12/312）、0.96%（3/312）,两组间比较差异有统计学意义（P〈0.01）;观察组剖宫产率78.8%（52/66）,阴道分娩率21.2%（14/66）,对照组剖宫产率为75.0%（234/312）,阴道分娩率25.0%（78/312）,两组间差异无统计学意义（P〉0.01）;观察组围产儿病死率18.1%（24/132）,新生儿窒息率44.7%（59/132）,对照组围产儿病死率为2.9%（18/624）,新生儿窒息率15.7%（98/624）,两组间比较差异有统计学意义（P〈0.01）;观察组胎儿畸形的发生率为3.7%（5/132）,显著高于对照组0.6%（4/624）。结论发育不同一性双胎妊娠主要的并发症（晚期流产、早产、羊水过多、双胎输血综合征、胎盘早剥、围产儿死亡、新生儿窒息和胎儿畸形）发生率明显高于发育一致双胎妊娠,临床上应给予重视,及时发现,及时诊断,适时终止妊娠以提高围产质量。     

成年双生子血压水平与DNA甲基化相关性研究

目的：在成年双生子人群中探索与血压指标（收缩压、舒张压、平均动脉压、脉压）存在相关性的DNA甲基化位点。方法：研究人群来自中国双生子登记系统,共476名双生子,问卷调查包括一般人口学特征、生活方式及疾病状况等信息,体格检查包括血压、身高、体重等信息,使用Infinium HumanMethylation450 BeadChip芯片对外周全血进行全基因组DNA甲基化检测。在调整潜在混杂因素的基础上,通过构建混合效应模型在全基因组范围寻找与血压指标存在相关性的DNA甲基化位点,显著性水平为错误发现阳性位点率<0.05。结果：经过数据质量控制最终纳入465名双生子（122对同卵双生子,104对异卵双生子,13对双生子的其中之一）,年龄(44.8±13.2)岁,男性多于女性,同卵略多于异卵,目前吸烟和目前规律饮酒者所占比例均大于30%。所有双生子个体均行全基因组DNA甲基化与血压指标相关分析,经多重校正后未发现显著的甲基化位点,但位于10号染色体的cg07761116在3个血压指标（收缩压、舒张压、平均动脉压）相关分析中的P值相对较小, 提示其可能是一个与血压相关的位点。还有7个位点在两个血压指标相关分析中的P值较小,所在基因与神经发育、蛋白质稳态、炎症反应等功能相关。结论：没有明确证据支持与血压水平存在相关性的甲基化位点,可能由于样本量不足等原因,可以为后续开展类似的双生子研究提供参考,后续研究可以关注10号染色体上的cg07761116及其他P值较小的位点。