高脂血症家族遗传因素与心血管病危险因素的聚集性研究

目的 探讨高脂血症家族遗传因素与心血管病危险因素个体聚集性的关系。方法 采用遗传流行病学研究方法,分析高脂血症先证者一级亲属与二级亲属心血管病危险因素的个体聚集性。其中,家族性混合型高脂血症家系15个（共93人）,家族性高胆固醇血症家系11个（共94人）。结果 超重、高收缩压、高舒张压、高apoB血症、高血糖、低水平高密度脂蛋白胆固醇,这6种高危因素中,心血管病危险因素的个体聚集性随着先证者亲属亲缘系数的下降而下降（P＜0．01）。结论 高脂血症家族遗传因素对心血管病危险因素的聚集起着重要作用。     

高血压家族遗传因素与心血管病危险因素聚集关系的研究

目的：探讨高血压遗传因素与心血管病危险因素聚集的关系。方法：采用家系调查方法，对比分析高血压家系和对照家系直系亲属的危险因素个体聚集性。共调查高血压家系２５个，含直系亲属１５８例，其中包括高血压患者５４例，血压正常者１０４例；对照家系１５个，含直系亲属６５人。结果：超重（体重指数＞２５ｋｇ／ｍ２），高甘油三酯（甘油三酯＞２．０ｍｍｏｌ／Ｌ），高尿酸血症（男：尿酸＞３７４．９ｍｍｏｌ／Ｌ；女：尿酸＞３１５．４ｍｍｏｌ／Ｌ），高胰岛素血症（胰岛素＞１２．２μｍｏｌ）及低高密度脂蛋白胆固醇（低高密度脂蛋白胆固醇＜０．９１ｍｍｏｌ／Ｌ）５个危险因素中，具有１个以上至５个以上上述危险者的年龄标化百分比在高血压家系明显高于对照家系，将高血压家系中高血压患者剔除后比较，这种规律依然存在。结论：高血压家族遗传因素可能对心血管病危险因素聚集起着重要的作用     

高脂血症家族遗传因素,超重对血脂水平的影响及其协同作用的研究

目的探讨遗传因素、超重及其相互作用对血脂水平的影响。方法采用家系调查法，于１９９６～１９９７年在北京地区搜集家族性高脂血症（混合型高脂血症家系和家族性高胆固醇血症家系）及正常对照家系共２５个进行统计分析。结果高脂血症家系血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平显著高于正常对照家系；调整其他危险因素后的血脂水平，高脂血症家系超重组＞高脂血症家系非超重组＞对照家系超重组＞对照家系非超重组。结论家族遗传因素和超重都是高脂血症重要的危险因素，二者具有协同作用。     

高脂蛋白(a)血症遗传模式及其遗传度的探讨

目的：探讨高脂蛋白（ａ）血症的家族聚集性、遗传模式及其遗传度。　　方法：采用遗传流行病学研究方法，对１３ 个高脂蛋白（ａ）血症家系（先证组，１０４ 人）及２６ 个正常对照家系（对照组，１５３人）以二项分布（ｐ＋ ｑ）ｎ 的数学模型及χ２ 检验判定家族聚集性。以Ｐｅｎｒｏｓｅ法和Ｆａｌｃｏｎｅｒ回归法进行遗传模式及其遗传度的估算。　　结果：先证组一级亲属患病率为３１．９４％ ，与对照组８．８２％ 相比，统计学差异具有显著性（Ｐ＜ ０．０１），将其按父母、同胞、子女分组分析，调整其它影响因素，先证组同胞中患病率显著高于对照组。二项分布显示，先证组实际频数大于二项分布的理论频数。　　结论：高脂蛋白（ａ）血症具有明显的遗传易患性，遗传度为９０．６％ ，属于多基因遗传模式     

血浆apoB100水平升高不宜作为家族性混合型高脂血症 与家族性高胆固醇血症鉴别诊断的指标

目的探讨家族性混合型高脂血症与家族性高胆固醇血症血浆载脂蛋白A1(apoA1)、载脂蛋白B100(apoB100)水平的异同。方法病例-对照/家系设计,家族性混合型高脂血症家系15个（93人）;家族性高胆固醇血症家系11个（94人）;对照家系12个（67人）。比较家系间及家系内受累组与未受累组血浆apoA1与apoB100水平。结果两种高脂血症家系间及两种家系内受累组间血浆apoA1与apoB100水平未见统计学显著性差异;与对照家系相比,两种高脂血症家系血浆apoB100水平均显著升高（P<0.01）,同时,家系内受累组血浆apoB100水平显著高于未受累组（P<0.01）。结论两种高脂血症家系受累组血浆apoB100水平均显著升高,故血浆apoB100水平升高不宜作为家族性混合型高脂血症与家族性高胆固醇血症鉴别诊断的指标。     

血浆apoB100水平升高不宜作为家族性混合型高脂血症与家族性高胆固醇血症鉴别诊断的指标

目的 探讨家族性混合型高脂血症与家族性高胆固醇血症血浆载脂蛋白A1（apoA1)、载脂蛋白B100（apoB100)水平的异同。方法 病例－对照／家系设计,家族性混合型高脂血症家系15个（93人）;家族性高胆固醇血症家系11个（94人）;对照家系12个（67人）。比较家系间及家系内受累组与未受累组血浆apoA1与apoB100水平。结果 两种高脂血症家系间及两种家系内受累组间血浆apoA1与apoB100水平未见统计学显著性差异;与对照家系相比,两种高脂血症家系血浆apoB100水平均显著升高（P＜0．01）,同时,家系内受累组血浆apoB100水平显著高于未受累组（P＜0．01）。结论 两种高脂血症家系受累组血浆apoB100水平均显著升高,故血浆apoB100水平升高不宜作为家族性混合型高脂血症与家族性高胆固醇血症鉴别诊断的指标。     

家族性高胆固醇血症患者低密度脂蛋白受体新突变类型与表型关系的研究

蔺洁 ,王绿娅 ,陈立伟 ,等 .中华心血管病杂志 ,2 0 0 4 ,(32 ) 6 :5 12 5 15　　家族性高胆固醇 (FH)作为冠心病的重要致病因素之一 ,已成为脂代谢和冠心病研究的热点 ,其发病机制是由于低密度脂蛋白受体基因突变 ,影响低密度脂蛋白受体与低密度脂蛋白结合 ,导致血浆胆固醇浓度升高并在组织内过度淤积。此研究是有关中国汉族家族性高胆固醇血症家系低密度脂蛋白受体 (LDLR)基因突变类型 ,研究基因型与表型间的关系 ,探讨FH发病的分子病理机制。先证者男性 ,10岁 ,自出生起身体多个部位逐渐出现结节 ;并有心绞痛发作。对先证者及家系成…     

家族性Graves''病和桥本甲状腺炎患者的家系调查

目的探索家族性Ｇｒａｖｅｓ’病（ＧＤ）和桥本甲状腺炎（ＨＴ）的遗传方式及发病相关性。方法按ＷＨＯ标准，诊断有ＧＤ或ＨＴ家族史的ＧＤ先证者２８１例，ＨＴ先证者８２例，与先证者性别、年龄相当的对照８００名，进行三代家族史和血统成员的调查研究。结果系谱分析显示：ＧＤ先证者家系组ＧＤ和ＨＴ的患病率是对照的９３．３倍和５．７倍（１９．６％对０．２１％和０．８０％对０．１４％），ＨＴ先证者家系组ＧＤ和ＨＴ的患病率（７．９％、１１．９％）是对照的３７．６倍和８５．０倍。ＧＤ先证者家系组与ＨＴ先证者家系组的一、二级亲属患ＧＤ的频率相近（１７．５％对１３．３％、５．７％对５．１％），且都极显著的高于对照组（０．２７％、０．２２％）。２２．４％ＧＤ先证者家系中患者数≥３，先证者同胞中，ＧＤ患病率为４５．９％。在双亲或其中之一为患者的３１个核心家系，ＧＤ符合常染色体显性（ＡＤ）遗传。家族性ＧＤ的遗传度为１２２．３±２．７７％。结论家族性ＧＤ和ＨＴ均为多基因遗传病，但ＧＤ有一个显性主基因存在，部分家系表现ＡＤ遗传。ＧＤ和ＨＴ的遗传基础有较多联系。     

先天性心脏病家族聚集的初步分析

目的 :对重庆地区先天性心脏病 (先心病 )的家系进行筛查 ,以探讨先心病家系的遗传模式。方法 :在群体调查中收集重庆地区先心病资料 ,对一个家系中有 2例及 2例以上先心病患者的高发家系绘制家系谱图 ,对先证者及其一、二和三级亲属成员逐个筛查 ,填写个案调查表 ,对高发家系进行分析。结果 :调查了 4 387个家系中有 2 1个高发家系 ,均无三级亲属 ,其中亲属患者的病种与先证者不完全一致 ,符合率为 33.33% (7/ 2 1)。先心病先证者的亲属患病率分别是一级亲属为 16 .4 9% (16 / 97) ,二级亲属为 1.89% (5 / 2 6 5 ) ,一、二级亲属患病率比较 ,差异有统计学意义 (χ2 =2 7.73,P <0 .0 1)。采用EmeryAEH分离分析法对高发先心病的遗传方式进行分析 ,结果符合常染色体单基因显性遗传 ,但同胞数不符合自然状态 ,故不能肯定其常染色体显性遗传方式 ;常染色体隐性遗传因剩下的家系样本太少 ,难以预测 ;而性连锁遗传中 ,Y连锁伴性遗传和X连锁遗传 ,与实际调查不符 ,可排除这种遗传方式。结论 :重庆地区先心病家系调查尚未发现地区差别 ,但有家族聚集现象 ,其亲属发病率高低与血缘关系近远相关 ,与先证者血缘关系越近的亲属患病率越高 ;同时 ,由于调查在独生子女或双胞胎中进行 ,不符合自然状态 ,为遗传流行病学     

家族性高胆固醇血症遗传筛查一家系

家族性高胆固醇血症（FH）是一种常见遗传病,以低密度脂蛋白胆固醇（LDL-C）水平升高为特征,伴早发动脉粥样硬化性心血管疾病。该文报道FH的一家系,先证者系12岁女性患者,血浆LDL-C异常升高、有黄色瘤且早发冠心病,符合纯合子FH（HoFH）或复合杂合子FH（CHeFH）的临床表现。采用下一代测序技术对该家系成员进行...     

Familial aggregation of coronary heart disease and its relation to known genetic risk factors

The question of how much of the familial aggregation of coronary heart disease is explained by familial clustering of coronary risk factors was approached by a case-control study involving 145 white male survivors of myocardial infarction, 145 age-matched white male blood donors, and the first-degree relatives of both groups. Certain risk factors such as serum cholesterol, triglyceride, and fasting blood glucose levels, blood pressure, and smoking history were determined in patients and control subjects. Relatives were interviewed. If the person was deceased, a copy of the death certificate was obtained. With the exception of high blood pressure, risk factors were significantly more frequent in patients than in control subjects.Among first-degree relatives of survivors of myocardial infarction, 16% had had a myocardial infarction, compared with 8.9% of relatives of control subjects. The frequency of coronary heart disease among first-degree relatives of patients and control subjects was 20.5 and 14.7%, respectively. To find out whether this higher frequency among relatives of patients was fully explained by the existence of known genetic risk factors among survivors of myocardial infarction, 2 approaches were taken. First, statistical analysis that eliminated the role of the various known genetic risk factors (by data stratification according to confounding risk variables and subsequent calculation of a pooled relative risk estimate according to the Mantel-Haenzel method) still indicated an approximately 2-fold (2.14) relative risk for myocardial infarction among families of survivors of myocardial infarction (and a risk of 1.71 for coronary heart disease). Similarly, another approach (Cox's life table regression analysis) confirmed that the classic risk factors could not predict familial occurrence.These results indicate that the familial aggregation of coronary heart disease is not entirely explained by the familial clustering of currently known coronary risk factors. Such familial aggregation could be caused by yet undefined genetic factors, by environmental factors common to family members, or by interaction of genetic factors with environmental agents.     

Coronary risk factors and the severity of angiographic coronary artery disease in members of high-risk pedigrees.

Affected members of early coronary pedigrees in Utah are at markedly increased risk for the development of clinical coronary heart disease (CHD). The relationship between the presence of coronary risk factors and the severity of angiographic coronary artery disease (CAD) in 53 members of high-risk Utah pedigrees was examined. Mean angiographic severity scores were higher in familial hypercholesterolemia or familial low high-density lipoprotein cholesterol (HDL-C) pedigrees than in type III hyperlipidemia or familial combined hyperlipidemia pedigrees. One sibling pair with hyperhomocyst(e)inemia had the highest mean angiographic severity scores. Clinical CHD (p less than 0.0001), increasing low-density lipoprotein cholesterol (LDL-C) (p = 0.0107), and decreasing HDL-C (p = 0.0068) were significant predictors of angiographic CAD severity. There appeared to be an interaction between gender and body mass index but not between gender and serum lipids in the prediction of angiographic CAD severity. Results of the present study in members of high-risk Utah pedigrees are consistent with results from other angiographic studies in non-high-risk persons. Of particular interest is the suggested independent predictive value of low HDL-C for angiographic CAD severity in members of high-risk pedigrees.     

Population-based frequency of dyslipidemia syndromes in coronary-prone families in Utah

The frequency of familial dyslipidemia syndromes was determined from blood tests in 33 objectively ascertained families with early coronary heart disease (CHD) (two or more siblings with CHD by the age of 55 years). Three fourths of persons with early CHD in these families had 90th percentile lipid abnormalities (cholesterol level at or above the 90th percentile, triglyceride level at or above the 90th percentile, and/or high-density lipoprotein cholesterol (HDL-C) level at or less than the 10th percentile). The HDL-C and triglyceride abnormalities were twice as common as low-density lipoprotein-cholesterol abnormalities. The most common syndromes found were familial combined hyperlipidemia (36% to 48% of families with CHD), familial dyslipidemic hypertension (21% to 54% of families with CHD), and isolated low levels of HDL-C (15%), with overlapping familial dyslipidemic hypertension with familial combined hyperlipidemia and low-level HDL-C. Well-defined monogenic syndromes were uncommon: familial hypercholesterolemia being 3% and familial type III hyperlipidemia, 3%. Another 15% of families with CHD had no lipid abnormalities at the 90th percentile. Physicians should learn to recognize and treat these common familial syndromes before the onset of CHD by evaluating family history and all three standard blood lipid determinations. Failure to recognize and treat them leaves affected family members at high risk of premature CHD.     

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus

BACKGROUND: The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young-onset diabetes from the Hong Kong Family Diabetes Study. METHODS: One hundred and seventy-nine families (913 subjects) were ascertained through a diabetic proband. Anthropometry, glucose homeostasis, blood pressure and lipid levels were examined. Familial aggregation and inter-relationships of these traits were examined by recurrence risk ratio, heritability, genetic and environmental correlations. RESULTS: One hundred and forty families (78%) had at least one subject with early-onset T2DM (age-at-diagnosis 相似文献   

阻塞性睡眠呼吸暂停低通气综合征并原发性高血压患者心血管事件危险因素分析

目的:探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)并原发性高血压(EH)发生心血管事件的危险因素。方法:收集213例阻塞性睡眠呼吸暂停低通气综合征并原发性高血压患者的临床资料,根据是否发生不良心血管事件将患者分为病例组(n=57)和对照组(n=156),对两组患者的临床资料进行单因素分析,多因素logistic回归分析OSAHS并EH发生不良心血管事件的危险因素。结果:57例(26.76%)患者发生不良心血管事件,病例组与对照组在性别、年龄、体质量指数(BMI)、家族遗传病史、饮酒史、血压分级、呼吸暂停低通气指数(AHI)、空腹血糖、总胆固醇等方面的差异有统计学意义(P均<0.05),logistic多因素回归分析显示,BMI(OR=1.898,95%CI:1.157~13.142,P=0.015)、年龄(OR=4.633,95%CI:0.563~15.236,P=0.042)、AHI(OR=9.789,95%CI:1.795~40.606,P=0.005)、空腹血糖(OR=5.082,95%CI:0.654~10.632,P=0.043)、总胆固醇(P=0.041,95%CI:1.114~87.431OR=10.892)是OSAHS并EH心血管事件发生的独立高危因素。结论:年龄、BMI、AHI、空腹血糖、总胆固醇是OSAHS并EH患者发生心血管事件的独立危险因素,建议对其进行有针对性的干预,以有效降低不良心血管事件的发生率。     

Cancer in the mothers and siblings of testicular cancer patients

Some families seem to have an increased risk of several different cancers and a reduced risk of others. Either genetic predisposition or a shared environment may explain this familial clustering, and the type of cause can affect how family members should be advised. We used data from a case-control study to examine the risk of cancer in the mother, sisters and brothers of men with testicular cancer. Our results show a significant relative risk (RR=1.7; 95% confidence interval (CI): 1.05-2.6) of cancer for sisters of testicular cancer patients in comparison with the sisters of controls. When data were combined for brothers and sisters, the RR for all cancers was 1.53 (CI: 1.1-2.3). Despite the limitations of our data, there is evidence for cancer clustering in the families of testicular cancer patients. Unfortunately, the evidence is consistent with either a genetic or environmental etiology.     

腰围甘油三酯指数与胸痛患者心血管危险因素聚集的关系

目的 研究腰围甘油三酯（WT）指数与胸痛患者心血管危险因素聚集的关系。 方法 回顾性分析在我院就诊的胸痛患者。比较心血管危险因素聚集组和非聚集组基线资料的差异。分析腰WT指数与心血管危险因素聚集的相关性。 结果 共有309例患者入选,其中女性115例。心血管危险因素聚集的检出率为73.8%。心血管危险因素聚集组的体重、腰围、体重指数、低密度脂蛋白胆固醇、甘油三酯、空腹血糖和腰WT指数均高于非聚集组（P<0.05）;高密度脂蛋白胆固醇低于非聚集组（P<0.05）。WT指数与心血管危险因素数量呈正相关（r=0.414,P<0.001）。多因素Logistic回归表明,WT指数是心血管危险因素聚集的独立预测因素（OR=1.012,95%CI：1.008~1.018）。WT指数在全部研究人群、男性人群及女性人群, ROC曲线下面积分别为0.750（95%CI：0.689~0.811）、0.709（95%CI：0.631~0.788）和0.852（95%CI：0.771~0.933）;其预测心血管危险因素聚集的最佳切点分别为138.7、110.6和134.4。 结论 WT指数是心血管危险因素聚集的独立预测因素,而且可以对心血管危险因素聚集做出定量的评价。     

Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype

This review provides an overview of the recent data evaluating triglyceride and low-density lipoprotein (LDL) size, two highly interrelated, genetically influenced, risk factors for cardiovascular disease (CVD). An examination of new epidemiologic studies continues to demonstrate that plasma triglyceride levels predict CVD. The first prospective study of the familial forms of hypertriglyceridemia has shown that relatives in familial-combined hyperlipidemia families are at increased risk for CVD mortality and that triglyceride levels predicted 20-year, CVD mortality among relatives in familial hypertriglyceridemia families. A meta-analysis of three, large-scale, prospective studies in men, and the first study to examine the correlation of LDL particle size distribution and vascular changes measured by B-mode ultrasound, add to growing evidence that small, dense LDL is atherogenic. Quantitative genetic analysis has recently shown substantial pleiotropic (common) genetic effects on triglyceride and LDL size. At least part of this may be explained by variation at the cholesterol ester transfer protein locus on chromosome 16, possibly through its role in reverse cholesterol transport. Taken together, these data provide new insights into the importance of triglyceride and LDL particle size for understanding genetic susceptibility to cardiovascular disease and its prevention.     

Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds

BACKGROUND & AIMS: Approximately 10% of pancreatic cancers are inherited, but the factors that affect tumorigenesis in familial pancreatic cancer are unknown. We sought to determine whether smoking or other factors could predict cancer risk in familial pancreatic cancer kindreds. METHODS: We conducted a nested case-control study including 251 members of 28 families. All families included 2 or more members with pancreatic cancer. We determined the effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number/standing of affected relatives on the risk of pancreatic cancer. RESULTS: Smoking was an independent risk factor for familial pancreatic cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.8-7.6), and the risk was greatest in males and subjects younger than 50 (OR, 5.2 and OR, 7.6, respectively). Smokers developed cancer 1 decade earlier than nonsmokers (59.6 vs. 69.1 years; P = 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4; 95% CI, 1.1-1.9 for each additional family member). Diabetes was not a risk factor for pancreatic cancer, although diabetes was associated with pancreatic dysplasia. One third of families demonstrated genetic anticipation, as the mean age of onset decreased by 2 decades between generations. CONCLUSIONS: Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly among males and those under age 50. Persons with multiple affected first-degree relatives are also at increased risk. These factors may be useful in selecting candidates for pancreatic cancer screening. Members of families with multiple pancreatic cancers should be counseled not to smoke.