Yunxian Yu

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (31)101.14 Total impact

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    ABSTRACT: In China, cardiovascular disease (CVD) risk reduction strategies are not systematically implemented in primary healthcare (PHC). We conducted an exploratory study to evaluate the preliminary effectiveness of our systematic CVD risk reduction package in one township hospital of Zhejiang.METHODS Using the Asian Equation, we selected subjects aged 40-74 years with a calculated 10-year CVD risk of 20% or higher from the existing resident health records and research checkup. The subjects were provided, as appropriate, with the low-dose combination of CVD-preventive drugs (antihypertensive drugs, aspirin, statin), lifestyle modification and adherence strategies monthly. The intervention was piloted for three months in 2012, preceding the conduct of a cluster-based randomized controlled trial (RCT).RESULTSA total of 153 (40%) subjects were recruited, with an average total 10-year risk of CVD of 28.5 ± 7.9%. After intervention, the appointment rate was up to 90%. An upward trend was observed for the use of CVD-preventive drugs. The smoking rates significantly reduced from 38 to 35%, with almost no change for salt reduction. The systolic blood pressure (BP) and diastolic BP decreased slightly.CONCLUSIONA holistic CVD risk reduction approach shows preliminary effects in a rural PHC setting of Zhejiang, China. However, further understanding is needed regarding its long-term effectiveness and feasibility in PHC practices. Our cluster-based RCT will provide the highest level of evidence for the policy development of preventing CVD in a rural PHC of China.
    Journal of Public Health 04/2014; · 2.06 Impact Factor
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    ABSTRACT: Maternal obesity is associated with a variety of common diseases in the offspring. One possible underlying mechanism could be maternal obesity induced alterations in DNA methylation. However, this hypothesis is yet to be tested. We performed epigenomic mapping of cord blood among 308 Black mother-infant pairs delivered at term at the Boston Medical Center using the Illumina HumanMethylation27 BeadChip. Linear regression and pathway analyses were conducted to evaluate the associations between DNA methylation levels and prepregnancy maternal BMI (<25, 25-30, ≥30 kg/m(2) ). The methylation levels of 20 CpG sites were associated with maternal BMI at a significance level of P-value <10(-4) in the overall sample, and boys and girls, separately. One CpG site remained statistically significant after correction for multiple comparisons (FDR corrected P-value = 0.04) and was annotated to a potential cancer gene, ZCCHC10. Some of the other CpG site annotated genes appear to be critical to the development of cancers and cardiovascular diseases (i.e., WNT16, C18orf8, ANGPTL2, SAPCD2, ADCY3, PRR16, ERBB2, DOK2, PLAC1). Significant findings from pathway analysis, such as infectious and inflammatory and lipid metabolism pathways, lends support for the potential impact of maternal BMI on the above stated disorders. This study demonstrates that prepregnancy maternal BMI might lead to alterations in offspring DNA methylation in genes relevant to the development of a range of complex chronic diseases, providing evidence of trans-generational influence on disease susceptibility via epigenetic mechanism. Environ. Mol. Mutagen., 2013. © 2013 Wiley Periodicals, Inc.
    Environmental and Molecular Mutagenesis 11/2013; · 3.71 Impact Factor
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    ABSTRACT: Cardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up. This is a prospective, open-label, cluster randomized controlled trial (RCT) with blinded data analysis. The trial will randomize 67 township hospitals with 31,708 participants in three counties in Zhejiang Province. Participants will be identified from existing health records and will comprise adults aged 50 to 74 years, with a calculated 10-year CVD risk of 20% or higher, or diabetes. In the intervention arm, participants will receive a package of interventions including: 1) healthy lifestyle counseling (smoking cessation, and salt, oil, and alcohol reduction); 2) prescription of a combination of drugs (antihypertensives, aspirin, and statin); and 3) adherence support for drug compliance and healthy lifestyle change. In the control arm, participants will receive usual care for hypertension and diabetes management at individual clinicians' discretion. The primary outcome is the incidence of severe CVD events over 24 months of follow-up. All CVD events will be defined according to the World Health Organization (WHO) monitoring of trends and determinants in cardiovascular disease (MONICA) definitions, diagnosed at the county hospital or higher level, and reported by the Zhejiang surveillance system. Secondary outcomes include: mean systolic and diastolic blood pressure, blood glucose, serum total cholesterol (TC), and adherence to appointments, and drugs and lifestyle changes. This trial focuses on risk reduction of CVD rather than specific diseases. It is not designed to compare therapeutic and healthy lifestyle interventions, but rather their combined effects in primary care settings. Through the trial, we intend to understand the effectiveness of the comprehensive CVD reduction package in routine practice. We also intend to understand the barriers and facilitators to implementing the package, and thus to advise on policy and practice change.Trial registration: Current Controlled Trials: ISRCTN58988083.
    Trials 10/2013; 14(1):354. · 2.21 Impact Factor
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    ABSTRACT: This study aims to evaluate perceived lifetime stress (LS), perceived stress during pregnancy (PS), chronic hypertension (CH) and their joint association with preeclampsia risk. This study includes 4,314 women who delivered a singleton live birth at the Boston Medical Center from October 1998 through February 2008. CH was defined as hypertension diagnosed before pregnancy. Information regarding LS and SP was collected by questionnaire. Preeclampsia was diagnosed by clinical criteria. LS, SP and CH were each associated with an increased risk of preeclampsia (OR(95%CI)=2.1(1.6-2.9) for LS; 1.7(1.3-2.2) for SP; 10.4(7.5-14.4) for CH). Compared to normotensive pregnancy with low LS, both normotensive pregnancy with high LS (2.1(1.6-2.9)) and pregnancy with CH and low LS (10.2(7.0-14.9)) showed an increased risk of preeclampsia, while pregnancy with high LS and CH yielded the highest risk of preeclampsia (21.3(10.2-44.3)). The joint association of SP and CH with preeclampsia was very similar to that of the joint association of LS and CH with preeclampsia. This finding indicates that high psychosocial stress and CH can act in combination to increase the risk of preeclampsia up to 20-fold. This finding underscores the importance of efforts to prevent, screen and manage CH, along with those to reduce psychosocial stress, particularly among women with CH.
    American journal of obstetrics and gynecology 07/2013; · 3.28 Impact Factor
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    ABSTRACT: The controversy that iodized salt may increase the risk of thyroid disorders has arisen in China during the past several years. This study aimed to explore whether iodized salt increased the risk of thyroid nodule among a Chinese population. A cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urinary iodine concentration (UIC), and thyroid nodule (by ultrasonography) were measured in 9412 adults. The associations of iodized salt with thyroid nodule were evaluated by using multiple mixed logistic regression models. The prevalence of thyroid nodule among men and women was 24.1% and 34.7%, respectively. Adults consuming noniodized salt had an increased risk of thyroid nodule (OR: 1.36; 95% CI: 1.01, 1.83). Similarly, compared with moderate salt appetite, mild salt appetite was associated with an increased risk of thyroid nodule among all adults (OR: 1.19; 95% CI: 1.03, 1.37) and among women (OR: 1.23; 95% CI: 1.03, 1.46). Furthermore, those who consumed neither iodized salt nor milk had a higher risk of thyroid nodule (OR: 1.72; 95% CI: 1.21, 2.43) than did those who consumed both iodized salt and milk. In addition, an increased risk of thyroid nodule (OR: 1.25; 95% CI: 1.07, 1.45) was observed among both pooled samples and women with low UIC. These findings indicate that low iodine intake may increase the risk of thyroid nodule in a Chinese population, particularly in women. Hence, the Universal Salt Iodization program may be indispensable for a coastal Chinese population such as that living in Hangzhou. This trial was registered at clinicaltrials.gov as NCT01838629.
    American Journal of Clinical Nutrition 07/2013; · 6.50 Impact Factor
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    ABSTRACT: Current cardiovascular disease (CVD) prevention is based on diagnosis and treatment of specific disease. Little is known for high risk people with CVD at the community level. In rural China, health records of all residents were established after the recent health reforms. This study aims to describe the characters of the rural population with high CVD risk regarding their clinical indicators, disease patterns, drug treatment and adherence. 17042 (87%) of all the 19500 rural residents in the two townships had valid health records in 2009. We employed a validated tool, the Asian Equation, to screen 8182 (48%) resident health records of those aged between 40-75 years in 2010. Those who were identified with a CVD risk of 20% or higher were selected for a face-to-face questionnaire survey regarding their diagnosed disease and drug treatment. 453 individuals were identified as high risk of CVD, with an average age of 53 years, 62% males, 50% smoking rate and average systolic blood pressure of 161 mmHg. 386 (85%) participated in the survey, while 294 (76%) were diagnosed with and 88 (23%) were suspects of CVD, hypertension, diabetes or hyperlipidaemia. 75 (19%) took drug regularly and 125 (32%) either stopped treatment or missed drugs. The most often used drugs were calcium channel blockers (20%). Only 2% used aspirins and 0.8% used statins. The median costs of drugs were 17 RMB (USD2.66) per month. The majority of the high risk population in our setting of rural China had already been diagnosed with a CVD related disease, but very few took any drugs, and less still took highly effective drugs to prevent CVD. A holistic strategy focused on population with high risk CVD and based on the current China public health reform is suggested in the context of primary care.
    PLoS ONE 01/2013; 8(1):e54169. · 3.73 Impact Factor
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    ABSTRACT: This study aims to explore the associations of polymorphisms in tachykinin, precursor 1 (TAC1), tachykinin receptor 1 (TACR1), and tachykinin receptor 2 (TACR2) genes and their interactions with the risk of colorectal cancer (CRC) among Chinese population. A population-based case-control study which included 394 cases and 393 cancer-free controls was carried out. A total of 19 tagSNPs in the three genes were chosen based on HapMap and NCBI datasets and genotyped by SNPshot assay. Multiple logistic regression models were applied to evaluate the associations of SNPs with CRC after adjustment for potential covariates. Furthermore, generalized multifactor dimensionality reduction (GMDR) method was used to test the interactive effect among three genes on CRC. Compared with those carrying rs3755457 CC/CT or rs12477554 TT/CT genotype, individuals carrying homozygous variants had higher risk of colorectal cancer (adjusted OR = 1.80, 95 % CI = 1.03-3.13, P = 0.039 for rs3755457; adjusted OR = 1.73, 95 % CI = 1.07-2.79, P = 0.024 for rs12477554). As for rs10198644, GG genotype was associated with a 1.72-fold (95 % CI = 0.37-0.88) decreased risk when compared with the common CC genotype. Moreover, the GMDR analysis indicated that the best interactive model included five polymorphisms: rs2072100 (TAC1), rs10198644 (TACR1), rs2193409 (TACR1), rs3771810 (TACR1), and rs4644560 (TACR2). Our study suggests that tachykinins pathway genes may participate in the development of CRC and the potential interactions among the three genes on CRC may exist, which has to be confirmed in future larger studies.
    International Journal of Colorectal Disease 06/2012; 27(11):1429-36. · 2.24 Impact Factor
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    ABSTRACT: Due to the high morbidity and mortality of colorectal cancer (CRC), this study aims to determine the joint association of RE-1-silencing transcription factor (REST) and nuclear factor-κB 1 (NFKB1) genes with CRC in a population-based study. A well-matched case-control study including 390 controls and 388 patients with CRC was enrolled in China. The selected single nucleotide polymorphisms (SNPs) in the REST and NFKB1 genes were genotyped by Illumina SnapShot Chip. After adjustment for important covariates, the associations of SNPs and joint association of REST and NFKB1 with CRC were evaluated by multiple logistic regression models. The subjects with the rs2228991 AA genotype of the REST gene had a decreased risk for CRC (OR = 0.38; 95%CI: 0.19-0.74), compared with the GG genotype. There were no significant associations between three SNPs in the NFKB1 gene, their haplotype and CRC risk. However, a significant combined effect of rs3774959 and rs3774964 in the NFKB1 gene with rs2228991 in the REST gene on CRC risk was observed. In conclusion, the present study found that mutation in the REST gene rather than the NFKB1 gene was associated with the risk of CRC. Furthermore, significant REST-NFKB1 joint association was observed for CRC, colon cancer and rectal cancer risk.
    Annals of Human Genetics 04/2012; 76(4):269-76. · 2.22 Impact Factor
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    ABSTRACT: The primary aim was to respectively evaluate PLA2G4A mutants modifying protective effect of tea consumption against colorectal cancer (CRC), colon and rectal cancer. All participants were recruited from January 2006 to April 2008. The information about tea consumption was collected by a structured questionnaire. CRC patients were diagnosed based on histology. Four single-nuclear polymorphisms (SNPs) in PLA2G4A gene were selected. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC, colon and rectal cancer. Three hundred patients with CRC and 296 controls well-matched were used in the final analyses. The significant individual associations between four SNPs (rs6666834, rs10911933, rs4650708 and rs7526089) and CRC were not observed. However, their CTAC haplotype was significantly associated with the increased risk of CRC (OR = 3.06; 95%CI = 1.52-6.19), compared with TCAC haplotype. Drinking tea was correlated with a decreased risk of CRC after adjustment for covariates (OR = 0.61; 95%CI = 0.39-0.97). Meanwhile, compared with no-tea drinkers with TT/CT genotype of rs6666834, tea drinkers with TT/CT or CC had significant lower risk of CRC (OR = 0.6, 95%CI = 0.36-1.00 for TT/CT; 0.38, 0.19-0.74 for CC). The joint effects between the remaining three SNPs and drinking tea on CRC were observed as well. Similar findings were observed on colon and rectal cancers. Tea consumption and haplotype of mutants in PLA2G4A gene were respectively associated with the risk of CRC. PLA2G4A mutants modified the protective effect of tea consumption against CRC, colon and rectal cancers in Chinese population.
    International Journal of Colorectal Disease 02/2012; 27(8):1005-13. · 2.24 Impact Factor
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    ABSTRACT: Populous, economically dynamic, and rapidly urbanizing, the Asia Pacific both reflects and strongly shapes trends in global public health. A comparative assessment of chronic disease prevalence, risk factors, and policy responses in nine Pacific Rim cities shows that chronic diseases are rapidly becoming the leading cause of morbidity and mortality even in the lower income cities of the Pacific Rim. Policy responses are heterogeneous, with few sufficiently funded or adequately informed by evidence. Much could be learned from comparative research and rigorous evaluation of prevention and control initiatives in this region.
    12/2010;
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    ABSTRACT: The xeroderma pigmentosum complementation group C (XPC) is responsible for removal of bulky helix-distorting DNA lesions. Several polymorphisms of XPC gene may modulate the colorectal cancer (CRC) susceptibility. We assessed the association of XPC Lys939Gln (A/C), Ala499Val (C/T), and PAT (−/+) polymorphisms with CRC risk in a population-based case–control study which included 421 CRC patients and 845 controls. For Lys939Gln, the CC genotype was associated with a significantly increased risk of CRC (odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.0−2.2) compared with the AA genotype. The subjects with PAT +/+ genotype had a significantly increased risk of CRC (OR = 1.5; 95% CI = 1.0−2.3), compared with those with PAT−/− genotype. Though no significant association between Ala499Val and CRC risk was observed, we found that individuals carrying the CT + TT genotypes showed a significantly decreased risk of rectal cancer (OR = 0.7; 95% CI = 0.5−1.0). Additionally, the haplotype C + C was associated with a significantly increased CRC risk (OR = 1.3; 95% CI = 1.0−1.6), compared with the most common haplotype A-T. Further, individuals with four or more risk alleles exhibited a significantly increased risk of CRC (OR = 1.4; 95% CI = 1.0−2.0), with a significant gene-dosage effect (P for trend = 0.038). Besides, never tea drinking was associated with a significantly increased risk of CRC (OR = 2.3; 95% CI = 1.7−3.3). Our results suggest that the XPC polymorphisms may modulate CRC susceptibility independently or jointly, and tea drinking has a protective effect on CRC. Mol. Carcinog. © 2010 Wiley-Liss, Inc.
    Molecular Carcinogenesis 11/2010; 50(3):189 - 198. · 4.27 Impact Factor
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    ABSTRACT: A randomized cluster trial was conducted to assess the impact of individualized health intervention guided by the transtheoretical model (TTM) theory on behavior change and quality of life (QoL) among the older rural population of China. A total of 2441 persons aged 60 years and over participated in the study. After a nine-month intervention, brined vegetable intake, salt intake, and smoking decreased (p < .001) while fresh vegetable and fresh fruit intake increased within the intervention group (p < .01) after adjusting for sociodemographic characteristics. The intervention group improved significantly in role-physical, role-emotional, mental health, and mental component summary scale scores (p < .05) after adjusting for sociodemographic characteristics, health behavior, and chronic disease status. The study shows that individualized health interventions are a feasible method of changing the health behaviors and improving the QoL in the older rural population of China.
    Educational Gerontology 10/2010; 36(10-11):919-939. · 0.39 Impact Factor
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    ABSTRACT: This study investigated whether high central adiposity was associated with prediabetes and decreased insulin sensitivity (IS) in both normal-weight (body mass index [BMI] <23 kg/m(2)) and overweight (BMI >or=23 kg/m(2)) rural Chinese women. Adipose variables measured by dual-energy x-ray absorptiometry (percentage body fat, percentage lower-body fat [%LF], and percentage trunk fat [%TF]) and general adipose variables (BMI and waist circumference) were used for examining the association of adiposity with prediabetes among 4071 rural Chinese women aged 20 to 60 years. Furthermore, the association of adiposity with IS was tested in both normal- and overweight women with normal glucose tolerance. BMI was highly correlated with percentage body fat and waist circumference, but was weakly correlated with %LF and %TF. Both high %TF (top quartile of %TF) and low %LF (lower 3 quartiles of %LF) were associated with higher prevalence of prediabetes in both normal- and overweight women. Compared with normal-weight women in low %TF, the odds of prediabetes were similarly increased for women with high %TF regardless of whether they were overweight (odds ratio [95% confidence interval] = 1.6 [1.3-2.0]) or not (odds ratio [95% confidence interval] = 1.5 [1.2-2.0]). Similarly, among 3280 women with normal glucose tolerance, high %TF was associated with increased fasting insulin, 2-hour oral glucose tolerance test insulin, and homeostasis model assessment of insulin resistance regardless of weight status (normal or overweight). Among relatively lean, rural Chinese women, high %TF was associated with increased odds of prediabetes and lower IS regardless of weight status (normal or overweight).
    Metabolism: clinical and experimental 07/2010; 59(7):1047-53. · 3.10 Impact Factor
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    ABSTRACT: We sought to determine whether placental markers of intrauterine inflammation were associated with poor weight gain among premature infants in the neonatal period. We reviewed 697 preterm births prospectively enrolled as part of an ongoing molecular epidemiological study. Placental markers and serial weight gain were analyzed for premature infants who were hospitalized for >/=21 days (N = 256). Placentas were examined for maternal inflammatory response (MIR), defined as subchorionitis, chorioamnionitis, deciduitis, or free membranitis, and fetal inflammatory response (FIR), defined as inflammation extending to the umbilical cord or chorionic plate. Multivariate linear regression and stratified analyses were performed. Decreases in weight gain at day 21 were associated with the presence of either MIR or FIR (beta coefficient = -4.63 +/- 1.41; P = .001). The association was stronger with FIR than MIR (P for trend = .0027) and persisted in the remaining hospitalized infants at day 28 (n = 223; beta coefficient = -5.53 +/- 1.85; P = .0028). Mean body weights were similar among the 3 groups by corrected age of 36 weeks or discharge, whichever came first. Associations between placental inflammation and poor growth persisted among infants with prenatal corticosteroid exposure and/or neonatal complications and remained marginally significant in the nonexposed groups. Among infants without intrauterine growth restriction, significant association persisted (n = 186; beta coefficient = -5.68 +/- 1.56; P = .0003). Placental inflammation is associated with poor neonatal growth. MIR and FIR may be useful markers for identifying infants at risk for postnatal growth failure.
    PEDIATRICS 03/2010; 125(4):e891-8. · 4.47 Impact Factor
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    ABSTRACT: In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5%, P < 0.001) to account for multiple comparisons. Among 506 births (GA 23-42 weeks), IL-1 beta increased with FIR among preterm subgroups (P = 0.0001 for <32 weeks; P = 0.0009 for 33-36 weeks). IL-6 and IL-8 increased with FIR among preterm and full-term infants (P < 0.0001). P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. We conclude that among 27 cord blood biomarkers, IL-1 beta, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 06/2009; 22(5):379-87. · 1.36 Impact Factor
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    ABSTRACT: In the United States, the rate of preterm delivery (PTD) is higher in African Americans (17.8%) than non-Hispanic whites (11.5%). Such disparity cannot be fully explained by differences in socioenvironmental factors. We genotyped 812 mothers in a case-control PTD study at Boston Medical Center who self-reported their ethnicity as "black." Regression analysis and Wilcoxon rank-sum test were applied to evaluate ancestral distribution and the association between genetic ancestry and PTD-related traits, as well as the potential confounding effect of population stratification. The estimated African ancestral proportion was 0.90 +/- 0.13. We found significant associations of ancestral proportion with PTD as a whole and PTD subgrouped by the presence of maternal hypertensive disorders. We did not observe significant confounding as a result of population stratification in this case-control PTD study. Our data underline the need for more intensive investigation of genetic admixture in African Americans to identify novel susceptibility genes of PTD.
    American journal of obstetrics and gynecology 06/2009; 201(1):94.e1-10. · 3.28 Impact Factor
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    ABSTRACT: The increasing prevalence of metabolic syndrome (MS) poses a serious public-health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high-density lipoprotein-cholesterol (HDL-C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00-0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL-C, and FPG. HDL-C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58-0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32-0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.
    Obesity 05/2009; 17(8):1581-7. · 3.92 Impact Factor
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    ABSTRACT: Inflammation has been associated with preterm delivery and adverse neonatal outcomes such as cerebral palsy and chronic lung disease. However, no study to date has simultaneously examined a wide range of inflammatory mediators and their relationship to gestational age. We sought to describe the distribution of immune biomarkers in cord blood across gestational age and to investigate the association between biomarker level patterns and preterm birth. As part of a large-scale molecular epidemiological study of preterm birth conducted at Boston Medical Center, this study analyzed both clinical and biomarker data from 927 births. Twenty-seven biomarkers were simultaneously quantified by immunoassay. The associations between the quartiles of 27 biomarkers and 3 gestational groups (< or =32, 33-36, and > or =37 weeks) were analyzed. Biomarkers found to be significant were further analyzed for dose-response correlation with preterm birth by logistic regression, adjusted for pertinent demographic and clinical factors. The 27 biomarkers could be classified into 1 of 3 groups: (1) biomarkers increased in preterm birth (interleukin [IL]-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, soluble IL-6 receptor alpha, tumor necrosis factor alpha, soluble tumor necrosis factor receptor I, and TREM-1 [triggering receptor expressed on myeloid cells 1]); (2) biomarkers decreased in preterm birth (brain-derived neurotrophic factor, IL-1beta, IL-18, matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony-stimulating factor, interferon gamma, macrophage migration inhibitory factor, neurotrophin 4, RANTES [regulated on activation, normal T-cell expressed and secreted], transforming growth factor beta, and tumor necrosis factor beta). Biomarkers have different directions of association with prematurity; for significant biomarkers, the strength of association increases with biomarker concentration. Our results provide important information that could be used to guide additional studies aimed at determining mechanisms that contribute to preterm birth.
    PEDIATRICS 05/2009; 123(5):1320-8. · 4.47 Impact Factor
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    ABSTRACT: Factor V (F5) genetic variants and maternal smoking during pregnancy individually has been associated with increased risk of preterm delivery (PTD). We hypothesize that F5 gene and maternal smoking may synergistically increase the risk of PTD. Three single nucleotide polymorphisms (SNPs) in F5 gene (rs6019, rs2213869 and rs6022) were genotyped in 542 mothers with PTD and 1,141 mothers with term deliveries at the Boston Medical Center. The individual and interactive effects of F5 SNPs and maternal smoking on PTD and gestational age were examined, respectively. The results suggested that maternal smoking, three F5 SNPs and F5 haplotype were individually associated with PTD and gestational age. More importantly, we found significant interactions between the two F5 SNPs (rs6019 and rs6022) and maternal smoking on PTD and gestational age. Compared with non-smoking mothers carrying rs6019 GG genotype, persistently smoking mothers carrying genotypes GC or CC were associated with significantly increased risk of PTD (OR(95% CI): 2.1(1.2-3.6) for GC; 5.7(2.1-15.0) for CC; p-interaction = 0.02). A significant interaction was also observed for gestational age. Similar pattern of interactions was found between rs6022 and maternal smoking on PTD. In summary, our data indicated that F5 gene variants and maternal smoking may synergistically increase the risk of PTD.
    Human Genetics 12/2008; 124(6):659-68. · 4.63 Impact Factor
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    ABSTRACT: Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case-control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8; 95% CI: 2.0-21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7-30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis.
    Human Genetics 06/2008; 123(4):359-69. · 4.63 Impact Factor

Publication Stats

278 Citations
75 Downloads
2k Views
101.14 Total Impact Points

Institutions

  • 2013
    • The Chinese University of Hong Kong
      • The Jockey Club School of Public Health and Primary Care
      Hong Kong, Hong Kong
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 2010–2013
    • Zhejiang University
      • School of Public Health
      Hangzhou, Zhejiang Sheng, China
  • 2008–2010
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 2007–2010
    • Northwestern University
      • • Department of Pediatrics
      • • Children's Hospital of Chicago Research Center
      Evanston, Illinois, United States
  • 2004–2008
    • Anhui Medical University
      Luchow, Anhui Sheng, China
  • 2006
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2004–2005
    • University of Science and Technology of China
      • School of Life Sciences
      Hefei, Anhui Sheng, China