CDH13 Genetic Polymorphisms, Adiponectin and Ischemic Stroke: a Chinese Family-based Sib-pair Study.

OBJECTIVE: To understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors. METHODS: We recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model. RESULTS: In individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001). CONCLUSION: CDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.

[Relationship between brachial-ankle pulse wave velocity and glycemic control of type 2 diabetes mellitus patients in Beijing community population].

OBJECTIVE: To explore the correlation between glycemic control of type 2 diabetes mellitus (T2DM) patients and brachial-ankle pulse velocity (baPWV). METHODS: A community-based cross-sectional study was conducted in Beijing, China. Every subject underwent physical examinations, glycated hemoglobin (HbA1c), blood lipid and baPWV measurements and completed a standardized questionnaire. T2DM patients were divided into well controlled and poorly controlled groups according to HbA1c levels. The correlation between glycemic control of T2DM patients and baPWV was analyzed. RESULTS: In this study, 1 341 subjects were recruited, including 733 T2DM patients and 608 non-diabetes subjects. Compared with non-diabetes subjects, abnormal baPWV (baPWV≥1 700 cm/s) rate for T2DM patients was higher (40.8% vs. 26.8%, P<0.001). With HbA1c<6.5% or <7.0% as the aim of glycemic control in T2DM patients, the abnormal baPWV rates for non-diabetes subjects, well controlled and poorly controlled T2DM patients were significantly different (non-diabetes vs. HbA1c<6.5% T2DM vs. HbA1c≥6.5% T2DM: 26.8% vs. 32.8% vs. 42.6%, P<0.001; non-diabetes vs. HbA1c<7.0% T2DM vs. HbA1c≥7.0% T2DM: 26.8% vs. 36.1% vs. 43.4%, P<0.001). After being adjusted for gender, age, smoking status, diabetes mellitus family history, T2DM duration, cardiovascular diseases (CVD), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), total triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), the Logistic regression models suggested that glycemic control status of T2DM patients was associated with abnormal baPWV. Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<6.5% T2DM patients and HbA1c≥6.5% T2DM patients were 0.927(95%CI 0.560-1.537) and 1.826 (95%CI 1.287-2.591). Compared with non-diabetes subjects, the ORs for abnormal baPWV in HbA1c<7.0% T2DM patients and HbA1c≥7.0% T2DM patients were 1.210 (95%CI 0.808-1.811) and 1.898 (95%CI 1.313-2.745). CONCLUSION: The glycemic control status of T2DM patients from communities is significantly associated with baPWV. Poor glycemic control is a risk factor for abnormal baPWV. Keeping HbA1c under control might lower the risk of cardiovascular diseases in T2DM patients.

Interaction of type 2 diabetes mellitus with chromosome 9p21 rs10757274 polymorphism on the risk of myocardial infarction: a case-control study in Chinese population.

BACKGROUND: Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population. METHODS: A hospital-based case-control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI. RESULTS: After adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95% CI:1.06-2.19, pa = 0.0227; ORa = 2.40, 95% CI:1.51-3.81, pa = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95% CI:2.56-7.47, padd < 0.0001). CONCLUSIONS: These results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.

Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China.

BACKGROUND: Mandibuloacral dysplasia type A (MADA) is a rare autosomal recessive disorder, characterized by growth retardation, skeletal abnormality with progressive osteolysis of the distal phalanges and clavicles, craniofacial anomalies with mandibular hypoplasia, lipodystrophy and mottled cutaneous pigmentation. Some patients may show progeroid features. MADA with partial lipodystrophy, more marked acral, can be caused by homozygous or compound heterozygous mutation in the gene encoding lamin A and lamin C (LMNA). MADA and Hutchinson-Gilford progeria syndrome are caused by the same gene and may represent a single disorder with varying degrees of severity. MAD patients characterized by generalized lipodystrophy (type B) affecting the face as well as extremities and severe progressive glomerulopathy present heterozygous compound mutations in the ZMPSTE24 gene. CASES PRESENTATIONS: We described a rare pedigree from Southern China, among them all three children presented with phenotypes of MADA associated progeria. The two elder sisters had developed severe mandibular hypoplasia associated progeria since the age of 1 year. The eldest sister showed a progressive osteolysis. The youngest son of 10 months showed severer lesions than those of his sisters at the same age, and presented possible muscle damage, and his symptoms progressed gradually. Three genes mutations including LMNA, ZMPSTE24 and BANF1 were tested in the family. LMNA gene sequencing revealed a homozygous missense mutation, c.1579C > T, p.R527C for all three siblings, and heterozygous mutations for their parents, whereas no mutations of ZMPSTE24 and BANF1 genes was detected among them. CONCLUSIONS: The same homozygous mutation of c.1579C > T of LMNA gene led to MADA associated progeria for the present family. The course of osteolysis for MADA is progressive.

The impact of lipid-metabolizing genetic polymorphisms on body mass index and their interactions with soybean food intake: a study in a Chinese population.

OBJECTIVE: To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake. METHODS: A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. RESULTS: The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15-2.34, P<0.01) after adjusting for the common confounders. CONCLUSION: Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.

[A matched case-control study of risk factors in abdominal aortic aneurysm].

OBJECTIVE: To examine the potential influence factors of abdominal aortic aneurysm (AAA). METHODS: A 1:2 pair-matched, case-control study was conducted from July 2011 to December 2012. A pair was composed of one AAA patient recruited from the Vascular Surgery Department, Chinese PLA General Hospital and two gender- and age-matched non-AAA subjects, one from the same hospital and the other from the community in Fangshan District in Beijing. Demographic data, medical history and the lifestyle of each subject were collected. Moreover, all the participants underwent abdominal ultrasound or computed tomography (CT) and peripheral venous blood samples were obtained. RESULTS: There were 155 case/control pairs. The multivariate conditional logistic regression model confirmed that suffering from hypertension conferred a 1.98-fold (95%CI 1.12-3.18) increased likelihood of AAA. Smoking was a strong independent risk factor of AAA, with odds ratios (95% confidence intervals) of 5.23 (2.44-11.23). Dyslipidemia (OR=2.61,95% CI 1.45-4.70), a higher level of serum hsCRP (OR=2.43,95%CI 1.37-4.31) and homocysteine (OR=2.73,95% CI 1.61-4.65) were all associated with AAA. CONCLUSION: Hypertension and smoking are the risk factors of AAA. Dyslipidemia, hsCRP and Hcy are associated with AAA.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Gender differences in demographic and clinical features and prescribing patterns of psychotropic medications in patients with major depressive disorder in China.

PURPOSE: Little is known about gender differences associated with major depressive disorder (MDD) in China. This study examined gender differences associated with other demographic and clinical characteristics and psychotropic drug treatment in Chinese patients with MDD. METHODS: A total of 1178 patients with MDD from 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide were enrolled. Cross-sectional data including patients' demographic and clinical characteristics and prescriptions of psychotropic medications were recorded using a standardized protocol and data collection procedure. RESULTS: The sample consisted of 793 female and 385 male patients. Univariate analyses revealed that male patients were younger than female patients, had a younger age of onset of depression, had less lifetime depressive episodes and had more bipolar features (i.e. patients who screened positive for hypomanic symptoms on the 32-item Hypomania Checklist, but did not meet the diagnostic criteria for DSM-IV bipolar disorders as measured by the Mini International Neuropsychiatric Interview). Also, men were more likely to be employed than women and less likely to have depressive episodes following stressful life events. In multivariate analyses, being employed, having bipolar features and not having depressive episodes following stressful life events were independently associated with being a male patient with major depressive disorder. There was no difference in use of psychotropic medications by gender. CONCLUSIONS: Most gender differences in MDD patients in this study are not consistent with findings of Western studies suggesting that gender differences in MDD may be determined by both biological and sociocultural differences among ethnically different patient populations.

Lack of association between genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19 and antituberculosis drug-induced liver injury in a community-based Chinese population.

The precise pathogenic mechanism of antituberculosis (anti-TB) drug-induced liver injury (ATLI) is poorly understood. It may be associated with drug-metabolizing enzymes, such as cytochrome P450 (CYP) 3A4, CYP2C9 and CYP2C19. The aim of the present study was to explore the role of tagging single nucleotide polymorphisms (tSNPs) of CYP3A4, CYP2C9 and CYP2C19 in the risk of ATLI in a population-based anti-TB treatment cohort. A nested case-control study was designed. Each ATLI case was matched 1 : 4 with controls on the basis of age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing and genotyped by TaqMan allelic discrimination technology. Eighty-nine patients with ATLI and 356 controls were included in the study. One tSNP in CYP3A4 (rs12333983), two in CYP2C9 (rs4918758, rs9332098) and two in CYP2C19 (rs11568732, rs4986894) were selected and genotyped. The minor allele frequencies of rs12333983, rs4918758, rs9332098, rs11568732 and rs4986894 were 36.0%, 41.4%, 1.1%, 5.7% and 35.7%, respectively, in the patients, compared with 31.7%, 42.9%, 3.4%, 8.9% and 35.1%, respectively, in the controls. No significant differences were observed in genotypes or allele frequencies of the five tSNPs between the two groups and none of the CYP2C9 or CYP2C19 haplotypes was significantly associated with the development of ATLI. Based on the Chinese anti-TB treatment cohort, we did not find a significant association between the risk of ATLI and genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19. None of the haplotypes exhibited a significant association with the development of ATLI in a Chinese tuberculosis population.

Effectiveness of an educational intervention to improve child feeding practices and growth in rural China: updated results at 18 months of age.

Inappropriate complementary feeding practices have led to, in part, significant disparities in growth and nutritional status between rural and urban children in China. A cluster-randomised, controlled trial was implemented in Laishui, China to assess the effectiveness of an educational intervention on caregivers' feeding practices and children's growth. Eight townships were randomly assigned to the intervention or control. Five hundred ninety-nine healthy infants were enrolled at 2-4 months old, and were followed up at ages 6, 9, 12, 15 and 18 months. The intervention group received information on enhanced home-prepared recipes and food preparation and hygiene through group training, counselling and home visit. Key outcomes were children's physical growth, caregivers' knowledge and behaviours on complementary feeding, and the infant and child feeding index (ICFI). Analysis was by intention to treat. The intervention group achieved better knowledge and practices related to complementary feeding, and significantly higher ICFI scores at each follow-up point. Children in the intervention group achieved higher z-scores for weight-for-age (WAZ) and weight-for-height (WHZ) than the control (0.18 vs. 0.01 and 0.49 vs. 0.19, respectively) at 18 months old, and were less likely to have stunted growth (odds ratio = 0.71, 95% confidence interval: 0.53-0.94). Mixed model showed that the intervention group achieved significantly better linear growth over time, including WAZ (P = 0.016), WHZ (P = 0.030) and HAZ (P = 0.078). These results indicated that an educational intervention delivered through local health services can enhance caregivers' knowledge and practices of complementary feeding and ultimately improve children's growth.

[Association study between PDE4D gene polymorphism and ischemic stroke].

OBJECTIVE: To investigate the linkage and association between rs966221 (SNP 83) in PDE4D gene with stroke and related traits in ischemic stroke families. METHODS: Ischemic stroke families including ischemic stroke patients and their siblings and/or parents were recruited. Generalized estimating equation (GEE) was used to adjust for with-in family correlations and other potential confounding factors. Non-parameter linkage analysis and family based association test (FBAT) were applied to explore the relationship between rs966221 polymorphism and ischemic stroke together with its related traits. RESULTS: In the study 276 ischemic stroke families with totally 776 participants were enrolled. Apolipoprotein B (apoB), carotid intima media thickness (cIMT), high-density lipoprotein cholesterol and blood pressure were associated with ischemic stroke. In family based association test, after being adjusted for related chronic diseases, rs966221 C allele was found to be associated with cIMT in the dominant model (P=0.019), TT genotype (P=0.019) and CT genotype (P=0.007) were associated with cIMT significantly. After being adjusted for potential confounding factors, evidence of linkage was observed for rs966221 with apoB (P<0.001), high-sensitivity C-reactive protein (P=0.003) and systolic blood pressure (P=0.036). CONCLUSION: Abnormal serum lipid, blood pressure and increasing cIMT were associated with ischemic stroke, and linkage was observed for with apoB, high-sensitivity C-reactive protein, and systolic blood pressure; rs966221 C allele was probably associated with cIMT.

Prescribing patterns of antidepressants, antipsychotics and mood stabilizers in bipolar patients misdiagnosed with major depressive disorder in China.

OBJECTIVE: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. METHODS: A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. RESULTS: Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1-2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04-2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1-7.2, p < 0.001), whereas patients with BD-II were more likely to receive mood stabilizers (OR 2.4, 95% CI 1.3-4.4, p = 0.003). There was no difference in the use of antidepressants (OR 1.1, 95% CI 0.8-1.5, p = 0.7) and antipsychotics (OR 1.3, 95% CI 0.9-1.9, p = 0.2) between BD-II and MDD. In addition, there was no difference between BD-I and BD-II in any use of antidepressants, antipsychotics and mood stabilizers. CONCLUSIONS: The prescription of antidepressants for BD patients misdiagnosed with MDD is very common, and only a very small proportion of patients received guideline-concordant treatment. Considering the potentially hazardous effects of inappropriate pharmacotherapy in this population, continuing education and training addressing the correct diagnosis of BD and rational use of psychotropic medications are needed in China.

[Mendelian randomization study of the relationship between high-density lipoprotein cholesterol and age-related macular degeneration].

OBJECTIVE: To explore genetic variants robustly associated with high-density lipoprotein cholesterol (HDL-C) by Mendelian randomization analysis and to examine its causal association with age-related macular degeneration (AMD). METHODS: AMD cases and controls were selected from several hospitals nationwide. Their AMD was diagnosed by eye examination, serum HDL-C levels were examined by blood tests, and other informations were also collected including demographic characteristics, high risk behaviors and so on. The genetic loci hepatic lipase gene (LIPC) rs10468017 was used as instrumental variables for HDL-C. RESULTS: The study population contained hospital-based 545 AMD patients and 480 controls. The LIPC genotypes were unrelated to all potentially confounding factors measured in this study. In conventional multivariable analyses, the HDL-C level was positively associated with AMD. The odds ratio was 2.00 (95%CI: 1.41-2.86). Instrumental variable analyses (Mendelian randomization approach) showed an increasing odds ratio of HDL-C and AMD, which was 7.15 (95%CI: 0.80-64.13). CONCLUSION: Being different with previous observational analysis, this study did not support the status of increasing serum HDL-C level as a risk factor for AMD by Mendelian randomization analysis.

[Case-control study of risk factors in age-related macular degeneration].

OBJECTIVE: To examine the potential influence factors of age-related macular degeneration (AMD). METHODS: A nationwide multicenter case-control study conducted between Jan. 2008 and May 2010. A total of 545 AMD patients and 480 controls, aged 50 years or older consented to participate in the study. Questionnaires were designed to collect information about demographic characteristics (age, gender), family history, disease history, and behavior factors (smoking, drinking). Moreover, physical examinations, biochemical examinations and ophthalmology examinations were conducted for each participant. RESULTS: The subjects who had AMD family history were 4.21 times more likely to have AMD (P<0.001). The subject who had the history of tracheitis /asthma were 1.87 times more likely to have AMD (P=0.008). Both smoking and drinking were risk factors to AMD (OR= 1.91,P < 0.001; OR=1.53, P = 0.003, respectively). Total protein (P = 0.004), high-density lipoprotein cholesterol ester (P = 0.016) and apolipoprotein A1 (P = 0.012) were associated with AMD. CONCLUSION: Family history, smoking, drinking and history of tracheitis /asthma are the risk factors of AMD. Total protein, high-density lipoprotein cholesterol ester and apolipoprotein A1 are associated with AMD.

Quality Evaluation and Reporting Specification for Real-World Studies of Traditional Chinese Medicine.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.

Design of the anti-tuberculosis drugs induced adverse reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS).

BACKGROUND: More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. METHODS/DESIGN: Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. DISCUSSION: ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.

[Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril].

OBJECTIVE: To explore the correlation of rs2106809 from angiotensin-converting enzyme 2 gene with antihypertensive effects of benazepril, as well as its interactions with polymorphisms of angiotensinogen(AGT) and angiotensin II type 1 receptor(AGTR1) gene. METHODS: Correlation between rs2106809 and blood pressure reduction was estimated based on a field trail with 1 831 hypertensive patients using benazepril for 2 weeks. Generalized multifactor dimensionality reduction (GMDR) was used to explore the interactions of rs2106809 and 8 single nucleotide polymorphisms (SNPs) of AGTR1 gene and 3 SNPs of AGT gene. RESULTS: rs2106809 was found to be associated with reduction in systolic blood pressure and pulse pressure in women, as well as pulse pressure reduction in men. T allele carriers presented more blood pressure reduction (1.4, 1.3 and 0.9 mmHg/T allele respectively). Gene-gene interactions involving rs2106809 were found in systolic blood pressure reduction of men, and the response to benazepril of non-sensitive genotypes carriers was 8.2 (95% confidence interval: 6.6-9.7) mmHg, lower than that of sensitive genotypes carriers. CONCLUSION: rs2106809 might act as an independent influencing factor or component of gene-gene interaction in blood pressure reducing effects of benazepril.

Family support and employment as predictors of smoking cessation success: a randomized, double-blind, placebo-controlled trial of nicotine sublingual tablets in chinese smokers.

BACKGROUND: The purpose of this study is to assess social support and demographic factors that influence the success of smoking cessation aided with sublingual nicotine tablets in a Han Chinese population. METHODS: We randomly allocated 211 Beijing residents who smoked >or= 10 cigarettes a day for at least 1 year into a double-blind, placebo-controlled 3-month randomized smoking cessation trial using sublingual nicotine replacement therapy (NRT). Self-reports of sustained smoking cessation were verified during the study by expired carbon monoxide concentrations and urine-cotinine concentrations. Logistic regression analysis used an intent to treat sample for sociodemographic associations with abstinence and reduction in smoking. RESULTS: The abstinence rates at the end of treatment for NRT vs. placebo were 52 % vs .19%, and smoking reduction (reduced to at least 50% of baseline) rates for NRT vs. placebo were 43% vs .15% for a total response rate with NRT of 95% for either stopping completely or reducing smoking by 50%. The only factor strongly associated with successful smoking cessation after 3 months of sublingual NRT was being married (adjusted odds ratio 2.18; 95%confidence interval 1.10-4.33). Smoking association, on the other hand, was associated with being married and with employment as a white collar worker (2.24; 1.03 to 4.86). CONCLUSIONS: These findings suggest the need for a more in-depth examination of the impact of being married and employment as a white collar worker (rather than manual laborer) in order to develop better targeted interventions for improving smoking cessation interventions.

[An association study of abdominal obesity and polymorphisms of UCP2 and SREBP1c genes].

OBJECTIVE: To investigate the association of -866A/G polymorphism of uncoupling protein 2 (UCP2) gene, and 54G/C polymorphism of sterol regulatory element binding protein 1c (SREBP1c) gene with abdominal obesity in the population of type 2 diabetes mellitus families. METHODS: Eligible type 2 diabetes mellitus cases from newly diagnosed and previous hospitalized patients were choson, then their family members (siblings and parents) tracked. A set of questionnaires was administered to obtain information on demographic characteristics. Physical measurements were recorded. DNA was extracted from blood samples and genotyped using polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). Generalized estimating equation (GEE) was used to adjust for within-family correlation in analysis of relationships of factors. RESULTS: In the study population, the frequency of A allele of UCP2-866A/G polymorphism was 0.459, and of G allele 0.541; the frequency of G allele of SREBP1c 54G/C polymorphism was 0.822, and of C allele 0.178. Totally 762 participants were analyzed using GEE regression. It was shown that the odds ratio (OR) of the population with only 54G/C polymorphism of SREBP1c gene being the mutant type (GC/CC) was statistically significant while -866A/G polymorphism of UCP2 gene not being the mutant type (AG/GG) was not. The OR of the population with the opposite genotype status was 1.8 (P=0.042), and that with mutant types of both polymorphisms 3.2(P=0.001). CONCLUSION: In the population of type 2 diabetes mellitus families, only 54G/C polymorphism of SREBP1c gene being the mutant type (GC/CC) might be a moderate risk factor of abdominal obesity. When both the two polymorphisms studied are the mutant type, the risk of abdominal obesity may increase significantly.

Association between short sleep duration and carotid atherosclerosis modified by age in a Chinese community population.

BACKGROUND AND AIM: Short sleep duration is a risk factor of cardiovascular disorder; however, the association between short sleep duration and carotid atherosclerosis has not been completely characterised. The aim of this study is to investigate the association between short sleep duration and carotid atherosclerosis. METHODS: We used the cross-sectional data collected between May 2014 and July 2014, which were based on a cardiovascular disease cohort study including 3798 participants aged 40 years and older who are residents of Beijing, China. We used logistic regression models to examine the associations between sleep duration and carotid atherosclerosis. RESULTS: After the adjustment of covariates, short sleep duration (less than 5 hours per night) was found to be associated with carotid atherosclerosis, and it also elevated the risk of, in both terms, the increment of prevalence (OR=1.31, P<0.05) and the quantity of carotid plaques (OR=1.28, P<0.05). When age was also taken into consideration, the largest association, in both terms of prevalence (OR=3.46, P<0.01) and the number of carotid plaques (OR=4.23, P<0.01), was found in subjects over the age of 60 with short sleep duration. CONCLUSION: In conclusion, sleep duration less than 5 hours per night is associated with a higher risk of carotid atherosclerosis compared with subjects who sleeps for 5 or over 5 hours per night, and the association may be modified by age.