粤籍汉族多囊卵巢综合征遗传流行病学研究

目的分析多囊卵巢综合征（PCOS）的遗传流行病学特征。方法采用调查表的方式对324例PCOS患者及其家系进行调查,同时结合临床检查。应用SPSS13.0软件、Falconer公式对资料进行统计学处理和分析。结果PCOS患者的月经稀发发生率为74.23%,高雄激素血症者占52.71%,卵巢多囊样改变者占93.27%;PCOS组及对照组一级亲属女性月经稀发发生率分别为17.81%和7.70%,男性早秃发生率为别为11.15%和5.33%,先证者家系的月经稀发和男性早秃患病率高于对照者家系;先证者一级亲属遗传度为44.91%。结论遗传因素在PCOS的发病中起着重要作用,但环境因素可能也起着重要的作用。     

多囊卵巢综合征家系遗传方式研究

目的 探讨多囊卵巢综合征（polycystic ovary syndrome,PCOS)的遗传方式。方法 采用遗传流行病学中的简单分离分析和综合分离分析方法。对139PCOS患者一级亲属中女性月经不规律和男性早秃的发生情况进行分离比分析。结果 女性月经不规律在患者母亲和姐妹中的发生率分别为37．4％和33．1％,男性早秃在患者父亲和兄弟中的发生率分别为19．4％和6．5％,简单分离分析显示PCOS在子代的分离比为0．3023,综合分离分析显示其符合共显性完全外显有散发遗传模型,纯合致病基因频率为0．046。结论 PCOS呈共显性遗传方式。     

多囊卵巢综合征生物样本库建设及管理

<正>多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄女性最常见的一种生殖内分泌疾病,影响世界5%~10%的育龄妇女~([1]),其临床表现呈多态性,包括月经紊乱或稀发、闭经,多毛和肥胖,伴卵巢多囊性增大等。PCOS与不孕和肥胖有关,可增加患Ⅱ型糖尿病、胰岛素抵抗、高血压、氧化应激、血脂异常和心血管等疾病的终身风险~([2]),PCOS的研究已经取得了很大的进展,但是发病机制至今不明,目前认为是环境~([3])和遗传因素~([4])的共同作用的结果。     

多囊卵巢综合征的研究进展

多囊卵巢综合征（PCOS）是由女性生殖内分泌和代谢功能异常导致的排卵障碍性疾病,在生育年龄妇女中发病率为5％-10％,在无排卵的不孕症患者中约占70％。临床表现呈多态性,包括月经稀发、闭经、不孕、肥胖、多毛、痤疮等。近几年研究发现,PCOS不仅影响患者生殖功能,还存在多方面的代谢障碍,PCOS的概念超出妇科内分泌的领域,成为一组累及多系统的慢性内分泌代谢疾病。     

女性乳腺癌的遗传流行病学研究

本文应用遗传流行病学方法对５个城市居民中的２３０例女性乳腺癌患者及其４６０名对照进行了调查，结果表明：女性乳腺癌患者一级亲属的女性乳腺癌发病率（２．０６％）显著高于对照者一级亲属的发病率（０．２３％，ＲＲ＝９．０６，９５％，ＣＩ＝３．０７－２６．６８）；用Ｆａｌｃｏｎｅｒ阈值模型估算出女性乳腺癌一级亲属的遗传度为５０．６６±６．１６％；并用多因素条件Ｌｏｇｉｓｔｉｃ回归模型在控制可能的混杂因素条件下，分析了影响乳腺癌发病的主要危险因素，结果显示礼腺癌家族史仍为有意义的因素。本文结果提示遗传因素为影响乳腺癌发病的重要危险因素，并与有关环境危险因素拟存在一定联系。     

多囊卵巢综合征诊断及分型的研究与进展

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是青春期及育龄期妇女最常见的一种内分泌紊乱性疾病,以月经稀发或闭经、临床上高雄表现或高雄激素血症和多囊卵巢作为特征,经常伴有胰岛素抵抗（IR）、代偿性高胰岛素血症和肥胖。临床表现有月经紊乱、稀发或闭经、多毛、黑棘皮现象、肥胖、不孕、双侧卵巢多囊样改变（PCO）等,     

冠心病患者体质量指数、皮褶厚度及肥胖的研究

目的了解冠心病患者的体质量指数和皮褶厚度特征,为早期干预提供依据。方法采用国际通用的人体测量法,测量了大连市区健康成人300名(健康男性和女性各150名)和冠心病患者310名(男性160名,女性150名)的身高、体质量和4项皮褶厚度,并利用体脂含量(F%)和体质量指数(BMI)法判定肥胖。结果男女冠心病患者的4项皮褶厚度、F%和BMI的平均值均大于健康成人。用F%法判定肥胖,健康成人和冠心病患者中肥胖比率男性分别为20%和56.25%,女性分别为10%和30%。用BMI法判定肥胖,健康成人和冠心病患者中肥胖比率男性分别为18%和53.75%,女性分别为8%和26%。结论冠心病患者的皮褶厚度较厚,肥胖比例明显高于健康人。     

强迫症临床亚型的研究

目的：探讨和区分出强迫症的临床亚型，及各亚型与药物治疗的关系。方法：采用临床研究与家系遗传研究相结合的方法，对９０例未服药的强迫症的临床特征、合并疾病、一级亲属的精神疾病发病情况及治疗反应进行研究。结果：单纯强迫观念组、强迫观念伴强迫行为组及伴有抽动障碍的强迫症组在临床特征、合并疾病、家系遗传及治疗反应等方面显示显著的差异。单纯强迫观念组具有较高的焦虑分，合并疾病及家系一级亲属中焦虑障碍明显高于其它两组，对氯丙咪秦的疗效达８７．１％，自知力完整，预后好。伴有抽动障碍的强迫症发病年龄早（１６．４岁），男性明显高于女性（１０∶１），合并疾病及一级亲属中的精神分裂症、抽动障碍及重性抑郁患病率明显增高，对氯丙咪秦的疗效差（３５．７％），社会功能受损重，预后差。强迫行为组临床特征介于二者之间。结论：这三组强迫症可能是不同的临床亚型且显示本病从神经症特征到精神病特征之间的连续谱     

Binswanger病遗传度的研究

为了探讨遗传因素在Ｂｉｎｓｗａｎｇｅｒ病中的作用，采用家系调查方法，对８２例Ｂｉｎｓｗａｎｇｅｒ病先证者作了１∶１的病例对照研究。结果提示先证者一级亲属标准化患病率（１０．３０％）明显高于对照者（２．８５％），遗传度为５４．３５％±８．２８％。男性和女性的患病率无明显差异。表明遗传因素在Ｂｉｎｓｗａｎｇｅｒ病中起着一定作用。     

多囊卵巢综合征患者的月经改变与血激素水平相关分析

目的探讨多囊卵巢综合征(PCOS)患者月经周期改变与血中睾酮、雄烯二酮和胰岛素水平的关系。方法选择临床诊断为PCOS的患者112例,包括继发闭经组(56例)和月经稀发组(56例),采用放射免疫法测定其血清性激素及空腹胰岛素水平,对比两组患者早卵泡期或闭经状态下各项性激素、空腹胰岛素水平及体重指数。结果继发闭经组患者的睾酮、雄烯二酮、空腹胰岛素水平显著高于月经稀发组(P=0.00,P=0.016,P=0.024)结论(1)继发闭经的PCOS患者体内的血清睾酮、雄烯二酮和空腹胰岛素水平明显高于月经稀发的PCOS患者,提示在育龄期继发闭经的P-COS患者有更严重的内分泌代谢失调。(2)育龄期妇女PCOS月经异常程度与体重无直接相关性,但体重指数与高胰岛素血症/高睾酮直接相关,而高胰岛素/高睾酮水平与月经异常程度相干,提示体重对月经异常可能有间接影响。     

Familial risk assessment for early-onset coronary heart disease.

PURPOSE: We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis. METHODS: By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2% CONCLUSIONS: Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.     

Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders, affecting 5-10% of the female population of reproductive age. "Classic" PCOS is characterized by clinical or biochemical hyperandrogenism and oligo-ovulation. According to the 2003 Rotterdam criteria, two additional phenotypes are recognized: (1) the ovulatory patient with androgen excess and polycystic ovarian morphology and (2) the anovulatory patient with polycystic ovarian morphology without androgen excess. PCOS is associated with an adverse cardiometabolic profile, consisting of increased total or central adiposity, increased blood pressure, a pro-atherogenic lipid profile, increased inflammatory markers, insulin resistance and abnormal glucose metabolism. Furthermore, the incidence of overt or gestational diabetes mellitus, as well as of preeclampsia is significantly higher in PCOS patients. Among the various PCOS phenotypes, those with evidence of androgen excess have the highest burden of cardiovascular risk. Studies evaluating the incidence of cardiovascular disease in postmenopausal women with PCOS are extremely sparse. The available data so far indicate that coronary heart disease, as well as cerebrovascular disease is more common in postmenopausal PCOS patients. Persisting high androgen levels through the menopause, obesity and maturity onset diabetes mellitus are proposed as the main mechanisms accounting for the increased risk.     

Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population

The aim of this study was to investigate the prevalence of diabetes mellitus, hypertension and cardiac complaints in a Dutch population with polycystic ovarian syndrome (PCOS) and to compare the results with the prevalence of these conditions in the Dutch female population, as retrieved from the Netherlands Health Interview Survey of Statistics Netherlands. A total of 346 PCOS patients were interviewed by telephone, with a mean age of 38.7 years (range 30.3--55.7) and a mean body mass index of 24.4 (range 17.5--55.8). Diabetes occurred in eight (2.3%), hypertension in 31 (9%) and cardiac complaints in three (0.9%) of the women. The prevalence of diabetes and hypertension differed significantly from the prevalence of these conditions in the Dutch female population (both P < 0.05). In PCOS women aged 45--54 years (n = 32) the prevalence of diabetes was four times higher (P < 0.05) and of hypertension 2.5 times higher (P < 0.01) than the prevalence of these conditions in the corresponding age group of the Dutch female population. Hypertension also occurred significantly (P < 0.05) more in the younger (35--44 years) PCOS group (n = 233), but this age group was significantly more obese (P < 0.01) when compared with figures of obesity of the Dutch female population. In conclusion, our data show that in a follow-up study of a relatively lean PCOS population, the prevalence of diabetes mellitus and hypertension was increased when compared with the Dutch female population, especially in women aged 45--54 years.     

Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease

OBJECTIVE: To test the hypothesis that polycystic ovary syndrome (PCOS) is associated with an increased risk of atherosclerotic cardiovascular disease (CVD) in older postmenopausal women. DESIGN: Cross-sectional study of community-dwelling non-estrogen-using postmenopausal-white women (N=713; mean+/-SD age, 73.8+/-7.9 years; mean body mass index, 24.0+/-3.5 kg/m) participating in the Rancho Bernardo Study. A putative PCOS phenotype was defined as the presence of three or more of the following features: (1) recalled history of irregular menses, (2) symptomatic premenopausal hyperandrogenism or biochemical evidence of current biochemical hyperandrogenism, (3) history of infertility or miscarriage, (4) central obesity, or (5) insulin resistance. Atherosclerotic CVD was determined from clinical history, electrocardiography, and structured interviews using validated techniques. The analysis was stratified by diabetes status, ascertained from medical history or 75-g oral glucose tolerance tests. RESULTS: The PCOS phenotype was present in 9.3% of the entire cohort and 5.8% of nondiabetic women. The prevalence of CVD was similar between women with the phenotype and unaffected women (27.3% vs 24.4%). Among women with intact ovaries and no diabetes, there was a stepwise graded association between an increasing number of features of the PCOS phenotype (ie, none to three or more) and prevalent CVD (P=0.02). A similar association was also observed for coronary heart disease alone (P=0.03). CONCLUSIONS: Among nondiabetic postmenopausal women with intact ovaries, prevalent atherosclerotic CVD is associated with features of a putative PCOS phenotype. This finding supports the thesis that PCOS increases the risk of atherosclerotic CVD after menopause.     

Polycystic ovary syndrome in men: Stein-Leventhal syndrome revisited

Polycystic ovary syndrome (PCOS), also referred to as Stein-Leventhal syndrome, is one of the most common endocrinopathies. It is characterized by hyperandrogenism, hyperinsulinemia, central obesity, polycystic ovaries, and anovulation. However, some of these manifestations, including the polycystic ovaries, are neither specific for the disorder, nor found in all affected individuals. PCOS appears to be due to one or more primary defects in the upstream gonadotropin/androgen and/or insulin pathway, with the polycystic ovaries being one of many downstream manifestations. Yet, the pathophysiology of PCOS is not completely elucidated. Since the primary defect underlying PCOS may be an upstream endocrine and/or metabolic disturbance, rather than a defect in the ovaries themselves, we hypothesize that this aberration can also arise in men and that the absence of polycystic ovaries in men with other stigmata of the disorder should not eliminate the diagnosis. Our hypothesis is supported by the observation that a genetic susceptibility to PCOS exists, and that PCOS-type manifestations are not limited to women. Indeed, male relatives may suffer from insulin resistance, obesity, diabetes mellitus, and cardiovascular disease. Therefore, recognition of this syndrome in men is important, since pharmacologic treatments identified for women with PCOS may alleviate metabolic problems related to insulin resistance and its sequelae in men with a similar underlying defect. We suggest that first-degree relatives of patients with PCOS should be examined not only for phenotypic features characteristic of PCOS but also for biochemical evidence of hyperinsulinemia and hyperandrogenism. In addition to examining these individuals for obesity, the women should be evaluated for hirsutism and the men should be screened for early-onset male-pattern alopecia and excess hairiness. Serologic evaluation should included the ratio of fasting levels of glucose to insulin, a glucose tolerance test, the free testosterone level and the sex hormone-binding globulin level. Finally, both male and female first-degree relatives of patients with PCOS should be tested for the underlying molecular defect(s) of this condition, once it is identified. As new treatments for PCOS emerge, e.g. insulin-sensitizing drugs, it will be important to determine if these treatments have beneficial effects on the metabolic symptoms and complications in all afflicted patients, regardless of gender.     

Expanding the definition of a positive family history for early-onset coronary heart disease.

PURPOSE: Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. METHODS: By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. CONCLUSIONS: Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.     

Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome

The aim of the study was to determine the prevalence of non-insulin dependent diabetes mellitus (NIDDM), arterial hypertension, coronary artery disease and the risk factors for these diseases in perimenopausal women with a history of polycystic ovary syndrome (PCOS) treatment. A group of 28 women was selected from a large group of patients who had undergone wedge ovarian resection. A total of 752 controls was selected by age (45-59 years) from a random female population sample. There was no difference between the two groups in body mass index, waist circumference or waist-hip ratio. Both groups were found to have identical family histories of NIDDM, hypertension, and coronary artery disease and identical smoking habits. We did not find a difference between the mean concentrations of lipids and fasting glucose. The two groups did not differ in the proportions of women with elevated lipid concentrations. The prevalence of NIDDM and coronary artery disease was significantly higher in PCOS women. In conclusion, women in the general population have the same level of risk factors at perimenopausal age as PCOS women. Patients with markedly expressed clinical symptoms of PCOS made up a subgroup in the general population at high risk for developing NIDDM and coronary artery disease.     

Left ventricular function in newly diagnosed non-insulin-dependent (type 2) diabetics evaluated by systolic time intervals and echocardiography

Systolic time intervals (STI) and echocardiography were recorded in 133 (70 men, 63 women) newly diagnosed non-insulin-dependent diabetics aged 45-64 years and in 144 (62 men, 82 women) non-diabetic control subjects of the same age. Both male and female diabetics had significantly increased pre-ejection period/left ventricular ejection time ratio (PEP/LVET) in STI as compared with the respective non-diabetic control subjects. Male diabetics showed a reduced ejection fraction (EF) in echocardiography, but no significant difference was found in this respect between female diabetics and controls. A significant negative correlation was found between 2-hour postglucose serum insulin level and EF in male and female diabetics. After adjusting for the effect of age, coronary heart disease, hypertension, obesity and haemoglobin concentration, male diabetics still had a higher PEP/LVET ratio and a lower EF than male controls. In women, no significant differences were found between diabetics and controls in the PEP/LVET ratio or EF adjusted for the above factors. The results of this study are compatible with the view that impaired left ventricular function may be an early phenomenon in the clinical course of non-insulin-dependent diabetes.     

Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome

BACKGROUND: The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). METHODS: A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. RESULTS: The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). CONCLUSION: The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.