Systematic Identification of Placental Epigenetic Signatures for the Noninvasive Prenatal Detection of Edwards Syndrome

Background: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21. Here we apply this epigenetic-genetic (EGG) chromosome dosage approach to detect Edwards syndrome (trisomy 18) in the fetus noninvasively. Principal Findings: We have systematically identified methylated fetal epigenetic markers on chromosome 18 by methylated DNA immunoprecipitation (MeDIP) and tiling array analysis with confirmation using quantitative DNA methylation assays. Methylated DNA sequences from an intergenic region between the VAPA and APCDD1 genes (the VAPAAPCDD1 DNA) were detected in pre-delivery, but not post-delivery, maternal plasma samples. The concentrations correlated positively with those of an established fetal genetic marker, ZFY, in pre-delivery maternal plasma. The ratios of methylated VAPA-APCDD1(chr18) to ZFY(chrY) were higher in maternal plasma samples of 9 male trisomy 18 fetuses than those of 27 male euploid fetuses (Mann-Whitney test, P = 0.029). We defined the cutoff value for detecting trisomy 18 fetuses as mean+1.96 SD of the EGG ratios of the euploid cases. Eight of 9 trisomy 18 and 1 of 27 euploid cases showed EGG ratios higher than the cutoff value, giving a sensitivity of 88.9% and a specificity of 96.3%. Conclusions: Our data have shown that the methylated VAPA-APCDD1 DNA in maternal plasma is redominantly derived from the fetus. We have demonstrated that this novel fetal epigenetic marker in maternal plasma is useful for the noninvasive detection of fetal trisomy 18. © Tsui et al.published_or_final_versio

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study

BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection

Associations between dietary habits and risk factors for cardiovascular diseases in a Hong Kong Chinese working population - The "Better Health for Better Hong Kong" (BHBHK) health promotion campaign

Diet and nutritional status have been shown to play pivotal roles in the occurrence of many chronic diseases. In this study, we examined the patterns of dietary habits and their relationships with risk factors for cardiovascular and chronic diseases in Hong Kong working populations. In April 2000, a 5-year territory-wide health promotion campaign supported by the Li Ka Shing Foundation was launched in Hong Kong by the Health InfoWorld of Hospital Authority. Between July 2000 and March 2002, 4841 Chinese subjects [2375 (49.1%) men and 2466 (50.9%) women, mean age: 42.4 ± 8.9 years (median: 43.0 years, range: 17-83 years)] from the general working class were recruited. Subjects were randomly selected using computer generated codes according to the distribution of occupational groups. A dietary questionnaire was used to assess 6 core dietary habits: daily fruit intake, vegetable intake, fluid intake, sugary drinks, regularity of daily meals and number of dining out each day. Overall, men had a worse cardiovascular risk profile and less desirable dietary habits than women. Those who had more unhealthy dietary habits were more likely to be obese and current smokers. Using logistic regression analysis with the dietary habits as independent variables, we found that obesity, smoking and constipation were independently associated with various unhealthy dietary patterns. In conclusion, there were close associations between dietary habits and risk factors for cardiovascular diseases in Hong Kong. More effective community education about healthy lifestyle is required in Hong Kong.link_to_subscribed_fulltex

Low levels of awareness of suboptimal health conditions in a high-risk working population: The "better health for better Hong Kong" health promotion campaign

The incidences of cardiovascular risk factors such as obesity and diabetes are rising in many Asian populations. In April 2000, a 5-year territory-wide health promotion campaign supported by Li Ka Shing Foundation was launched in Hong Kong by the Health InfoWorld of Hospital Authority. From the general working class, 4,832 Chinese people were randomly recruited into this campaign. There were 2,370 men (49.0%) and 2,462 women (51.0%; median age = 43.0 years, range = 17-83 years). Of these, 37.5% were obese (BM1 ≥ 25 kg/m 2 or waist circumference ≥80 cm in women and ≥90 cm in men), 22.3% had hypertension, 11.6% were smokers, 31.0% had hypercholesterolaemia (total cholesterol ≥5.2 mmol/l), 2.2% had diabetes, and 0.7% had a past history of cardiovascular disease. There were 1,338 participants (27.7%) who had 2 or more risk factors (more men than women: 36.9% vs. 18.9%, p < .001). Despite this high prevalence of multiple risk factors, most (83.1%) perceived their health status as satisfactory (more men than women: 85.6% vs. 80.7%, p < .001). In conclusion, the combination of high prevalence of multiple risk factors and low levels of awareness of their suboptimal health status herald a looming epidemic of life-threatening diseases in a group of middle-aged Hong Kong people. Massive public education is an important and essential, although it may not be self-sufficient, factor to reduce the socioeconomic impacts of this epidemic. Copyright © 2007 by Lawrence Erlbaum Associates, Inc.link_to_subscribed_fulltex

Serum amyloid A is not useful in the diagnosis of severe acute respiratory syndrome [3]

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Association between sleeping hours, working hours and obesity in Hong Kong Chinese: The 'better health for better Hong Kong' health promotion campaign

Objective: To study the inter-relationships between sleeping hours, working hours and obesity in subjects from a working population. Research design: A cross-sectional observation study under the 'Better Health for Better Hong Kong' Campaign, which is a territory-wide health awareness and promotion program. Subjects: 4793 subjects (2353 (49.1%) men and 2440 (50.9%) women). Their mean age (±s.d.) was 42.4±8.9 years (range 17-83 years, median 43.0 years). Subjects were randomly selected using computer-generated codes in accordance to the distribution of occupational groups in Hong Kong. Results: The mean daily sleeping time was 7.06±1.03 h (women vs men: 7.14±1.08 h vs 6.98±0.96 h, P=0.001). Increasing body mass index (BMI) was associated with reducing number of sleeping hours and increasing number of working hours reaching significance in the whole group as well as among male subjects. Those with short sleeping hour (6 h or less) and long working hours (>9 h) had the highest BMI and waist in both men and women. Based on multiple regression analysis with age, smoking, alcohol drinking, systolic and diastolic blood pressure, mean daily sleeping hours and working hours as independent variables, BMI was independently associated with age, systolic and diastolic blood pressure in women, whereas waist was associated with age, smoking and blood pressure. In men, blood pressure, sleeping hours and working hours were independently associated with BMI, whereas waist was independently associated with age, smoking, blood pressure, sleeping hours and working hours in men. Conclusion: Obesity is associated with reduced sleeping hours and long working hours in men among Hong Kong Chinese working population. Further studies are needed to investigate the underlying mechanisms of this relationship and its potential implication on prevention and management of obesity. © 2007 Nature Publishing Group All rights reserved.link_to_subscribed_fulltex

Proteomic profiling in SARS: Diagnostic and prognostic applications

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Detection of SARS Coronavirus RNA in the Cerebrospinal Fluid of a Patient with Severe Acute Respiratory Syndrome

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Serum proteomic fingerprints of adult patients with severe acute respiratory syndrome

Background: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease. Methods: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry. Results: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c α chain (m/z 28 119) and an internal fragment of fibrinogen α-E chain (m/z 5908). Immunoglobulin κ light chain (m/z 24 505) positively correlated with viral load. Conclusions: Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity. © 2006 American Association for Clinical Chemistry.link_to_subscribed_fulltex