Association between insomnia and type 2 diabetes:A two-sample Mendelian rando-mization study / 北京大学学报(医学版)

Objective:To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.Methods:We identified strong,independent single nucleotide polymorphisms(SNPs)of insomnia from the most up to date genome wide association studies(GWAS)within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus.After excluding SNPs that were significantly associated with smoking,physical activity,alcohol consumption,educational attainment,obesity,or type 2 diabetes mellitus,we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting(IVW)method.Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association.We calculated the F statistic of the selected SNPs to test the applicability of instrumental variable and F statistic over than ten indicated that there was little possibility of bias of weak instrumental variables.We further examined the existence of pleiotropy by testing whether the intercept term in MR-Egger regression was significantly different from ze-ro.In addition,the leave-one-out method was used for sensitivity analysis to verify the stability and relia-bility of the results.Results:We selected 248 SNPs independently associated with insomnia at the genome-wide level(P＜5 ×10-8)as a preliminary candidate set of instrumental variables.After clum-ping based on the reference panel from 1000 Genome Project and removing the potential pleiotropic SNPs,a total of 167 SNPs associated with insomnia were included as final instrumental variables.The F statistic of this study was 39.74,which was in line with the relevance assumption of Mendelian randomi-zation.IVW method showed insomnia was associated with higher risk of type 2 diabetes mellitus that po-pulation with insomnia were 1.14 times more likely to develop type 2 diabetes mellitus than those without insomnia(95％CI:1.09-1.21,P＜0.001).The weighted median estimator(WME)method and MR-Egger regression showed similar causal effect of insomnia on type 2 diabetes mellitus.And MR-Egger re-gression also showed that the effect was less likely to be triggered by pleiotropy.Sensitivity analyses pro-duced directionally similar estimates.Conclusion:Insomnia is a risk factor of type 2 diabetes mellitus,which has positively effects on type 2 diabetes mellitus.Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.

Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China / 中华流行病学杂志

Family-based cohort study is a special type of study design, in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted. Family-based cohort study can be applied to explore the effect of genetic factors, environmental factors, gene-gene interaction, and gene-environment interaction in the etiology of complex diseases. This paper summarizes the objectives, methods and results, as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.

Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China / 中华流行病学杂志

Family-based cohort study is a special type of study design,in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted.Family-based cohort study can be applied to explore the effect of genetic factors,environmental factors,gene-gene interaction,and gene-environment interaction in the etiology of complex diseases.This paper summarizes the objectives,methods and results,as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.

Serum High-Sensitive C-Reactive Protein Level and CRP Genetic Polymorphisms Are Associated with Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) development involves an inflammatory process with a potential genetic background. C-reactive protein (CRP) is an acute phase protein and was elevated in patients with AAA. The aim of this study was to investigate the association among serum high-sensitive CRP (hsCRP) concentration, its CRP genetic polymorphisms, and AAA. METHODS: Serum hsCRP concentrations and abdominal aorta diameters were measured, and correlation analysis between them was performed in 155 unrelated participants with AAA and 310 non-AAA controls. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1417938, rs1130864, rs1205, rs1800947) were identified via HapMap. Stratification analysis was performed to evaluate the effects of SNPs on the concentration of serum hsCRP. The association between 4 SNPs and AAA was assessed by unconditional logistic regressions. RESULTS: Elevated serum hsCRP level was found to be an independent risk factor for AAA (odds ratio [OR] = 3.91, 95% confidence interval [CI]: 2.45, 6.23) after adjustment for confounding factors. Concentrations of serum hsCRP were significant different (P = 0.01) in 4 subgroups derived from participants with abdominal aorta diameter <20 mm, 20-29 mm, 30-54 mm, and ≥55 mm. Stratification analysis revealed there was significant high frequency of elevated hsCRP levels in subjects carrying rs1205-CC genotype compared with those carrying rs1205-TT or CT genotypes (P = 0.004, OR = 2.31, 95% CI: 1.30, 4.11), suggesting that the genotype CC of rs1205 was associated with higher serum hsCRP levels. However, the frequency of rs1205-CC in AAA patients (15.3%) was similar to control subjects (17.6%), and we could not confirm rs1205-CC was the genetic risk factor of AAA (OR = 1.18, 95% CI: 0.69, 2.01). Moreover, we found another CRP polymorphism rs1417938-TT had a significantly higher likelihood of AAA than the AT genotype (OR = 2.07, 95% CI: 1.06, 4.03) for the first time, indicating there was perhaps a role for rs14117938-T polymorphism that correlates with AAA. CONCLUSIONS: Serum hsCRP may be related to the presence of AAA and abdominal aorta diameter. Genetic polymorphisms in CRP gene could influence the concentration of serum hsCRP and the likelihood of AAA, but the causal relationship between AAA and CRP should be demonstrated further.

Relationship between type 2 diabetes mellitus and serum stromal cell derived factor 1 levels / 实用医学杂志

Objective To explore the relationship between type 2 diabetes mellitus(T2DM)and serum stromal cell derived factor-1(SDF-1)levels. Methods A community-based epidemiological field study for T2DM patients and non-T2DM subjects was conducted in Beijing,China. Every subject underwent physical examinations, biochemical tests of stromal cell derived factor 1 and so on,and completed a standardized questionnaire. A total of 756 subjects were recruited in our analysis ,including 267 T2DM patients and 489 non-T2DM subjects ,T2DM patients were further divided into 81 simple T2DM patients and 186 macrovascular complication patients on the basis of the status of macrovascular complication. The correlation between serum SDF-1 levels and T2DM was analyzed. Results Compared with non-T2DM group,the level of SDF-1 in T2DM group was higher(P=0.019). The level of SDF-1 in simple T2DM group was also higher than macrovascular complication group(P=0.044). In the multi-ple linear regression analysis,after adjustment for age,gender,smoking,drinking,dyslipidemia,hypertension and BMI,SDF-1 level in simple T2DM group was higher than macrovascular complication group(P = 0.049), still. Conclusions Simple T2DM patients had a higher serum SDF-1 level than T2DM patients with macrovascular complications as well as those who did not suffer T2DM,suggesting that the stromal cell derived factor-1 may play a certain role in the development of T2DM and macrovascular complications.

Relationship between type 2 diabetes mellitus and serum stromal cell derived factor 1 levels / 实用医学杂志

Objective To explore the relationship between type 2 diabetes mellitus(T2DM)and serum stromal cell derived factor-1(SDF-1)levels. Methods A community-based epidemiological field study for T2DM patients and non-T2DM subjects was conducted in Beijing,China. Every subject underwent physical examinations, biochemical tests of stromal cell derived factor 1 and so on,and completed a standardized questionnaire. A total of 756 subjects were recruited in our analysis ,including 267 T2DM patients and 489 non-T2DM subjects ,T2DM patients were further divided into 81 simple T2DM patients and 186 macrovascular complication patients on the basis of the status of macrovascular complication. The correlation between serum SDF-1 levels and T2DM was analyzed. Results Compared with non-T2DM group,the level of SDF-1 in T2DM group was higher(P=0.019). The level of SDF-1 in simple T2DM group was also higher than macrovascular complication group(P=0.044). In the multi-ple linear regression analysis,after adjustment for age,gender,smoking,drinking,dyslipidemia,hypertension and BMI,SDF-1 level in simple T2DM group was higher than macrovascular complication group(P = 0.049), still. Conclusions Simple T2DM patients had a higher serum SDF-1 level than T2DM patients with macrovascular complications as well as those who did not suffer T2DM,suggesting that the stromal cell derived factor-1 may play a certain role in the development of T2DM and macrovascular complications.

Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus / 北京大学学报(医学版)

Objective: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients.Methods: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use.Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI.Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels.Logistic models were applied in multiple analysis adjusting for possible confounders.Results: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years.Among them, 78.3% were on hypoglycemic therapy.The cutoff points of quartiles of VAI were calculated for the males and females, respectively.According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e.Q1, Q2, Q3, and Q4.The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001).After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM.Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128to 2.088), respectively (trend P=0.003).With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282).Conclusion: The glycemic control among the patients with T2DM is significantly associated with VAI.High level of VAI is an indicator of poor glycemic control.

Relationship between brachial-ankle pulse wave velocity and glycemic control of type 2 diabetes mellitus patients in Beijing community population / 北京大学学报(医学版)

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-sec-tional study was conducted in Beijing, China. Every subject underwent physical examinations, glycated hemoglobin ( HbA1 c ) , blood lipid and baPWV measurements and completed a standardized question-naire. 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 sub-jects. 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 ad-justed 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 lipo-protein 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 HbA1 c <6 . 5% T2 DM patients and HbA1 c≥6 . 5% T2 DM 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 con-trol status of T2DM patients from communities is significantly associated with baPWV. Poor glycemic con-trol is a risk factor for abnormal baPWV. Keeping HbA1c under control might lower the risk of cardiovas-cular diseases in T2DM patients.

Risk factors of suicidality in major depressive disorder patients with and without anxious characteristics / 中国心理卫生杂志

Objective:To compare the suicidality risk in major depressive disorder (MDD)patients with and without anxious characteristics,and analyze the risk factors of suicidality in MDD patients. Methods:This was a secondary analysis of the data from the Diagnostic Assessment Service for people with Bipolar Disorders in China (DASP),which was initiated by the Chinese Society of Psychiatry (CSP),from September 1,2010 to February 28, 201 1. Based on the anxious module and suicide module of Mini International Neuropsychiatric Interview (M. I. N. I),1 172 MDD patients were classified as suffering from anxious MDD (n=728,62. 1%)and non-anxious MDD(n=444,37. 9%). Logistic regression was employed to examine the risk factors of suicidality in MDD pa-tients. Results:Among the anxious MDD patients,331 (45. 5%)of them had suicidality risk. And 54(12. 2%)of non-anxious MDD patients had suicidality risk. Compare to the non-anxious group,the anxious MDD patients had significantly higher suicidality risk (P<0. 00 1 ). Logistic regression analysis showed that more frequent depressive episodes (OR=2. 07 ),depressive episodes with psychotic symptoms (OR=2. 0 1 ),comorbid with anxious charac-teristics (OR=3. 18)or melancholic characteristics (OR=2. 90)were associated with suicidality risk in patients with MDD. Conclusion:It indicates that the anxious MDD patients may have higher suicidality risk than non-anx-ious MDD patients,and more frequent depressive episodes,depressive episodes with psychotic symptoms,comorbid with anxious characteristics or melancholic characteristics may be risk factors of suicidality in patients with MDD.

Study on the association between leukotriene A4 hydrolase gene polymorphism and ischemic stroke / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the association between polymorphism of leukotriene A4 hydrolase (LTA4H) gene among ischemic stroke patients and the related subtypes in the discordant sib pairs.</p><p><b>METHODS</b>Families including ischemic stroke patients and their siblings were recruited. Four single nucleotide polymorphisms (SNPs) of LTA4H as rs2072512, rs2540489, rs2540500 and rs6538697 were selected. Generalized estimating equation (GEE) was used to adjust for in-family correlation in the analysis of discordant sib pairs. Conditional logistic regression model and family based association test (FBAT) were both used to test the associations of LTA4H gene with ischemic stroke and its subtypes.</p><p><b>RESULTS</b>In total, data from 356 discordant sib pairs from 234 ischemic stroke patient pedigrees were analyzed. Results of GEE showed that hypertension, diabetes mellitus and hyperlipoidemia were associated with ischemic stroke. According to the association test results, rs2540489 G allele was found to be associated with ischemic stroke, both in the additive model (OR = 0.62, 95% CI: 0.41-0.94) and in the recessive model (OR = 0.48, 95% CI: 0.23-1.02). For two main ischemic stroke subtypes, rs2540489 G allele was found to be associated with large-artery atherosclerosis stroke in the additive model (OR = 0.48, 95% CI: 0.24-0.95) and in the recessive model (OR = 0.25, 95% CI: 0.07-0.93). After adjusting age, sex and other factors, the associations mentioned above, still existed.</p><p><b>CONCLUSION</b>rs2540489 polymorphism in LTA4H gene seemed to be associated with large-artery atherosclerosis stroke.</p>

A matched case-control study of risk factors in abdominal aortic aneurysm / 北京大学学报(医学版)

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 ultra-sound 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 hs-CRP (OR=2.43,95%CI 1.37-4.31) and homocysteine (OR=2.73,95%CI 1.61-4.65) were all asso-ciated with AAA.Conclusion: Hypertension and smoking are the risk factors of AAA .Dyslipidemia, hsCRP and Hcy are associated with AAA .

Expression of Toll-like receptors in the lesions of condyloma acuminatum / 中华微生物学和免疫学杂志

Objective To investigate the expression of Toll-like receptors(TLRs) in condyloma acuminatum(CA) lesions and their possible roles in the pathogenesis of CA. Methods The expressions of TLR1-10 mRNA level in the lesions of CA and in the cervix scrape cells from the patients with human papillomavirus(HPV) negative chronic cervicitis were detected by real-time quantitative fluorescent PCR. HPV typing was detected by HPV GenoArray test kit. Results Low-risk HPV type 6 and type 11 were the most prevalent types in the forty CA cases with positive rate of 77.5% and 55% respectively. 55% CA patients were found infected with more than two types of HPV. 35% CA patients were concurrently infected with high-risk HPV. The expressions of TLR3, 7, 8 mRNA were higher than other TLRs and the expression of TLR9 mRNA was lower than others in the lesions of CA. No significant differences of the TLR1-10 mRNA levels were found between HPV6 and HPV11 positive CA lesions, so did it between low-risk and high-risk HPV concurrent infected CA lesions. The expressions of TLR1-3, TLR5-8, TLR10 mRNA, especially TLR2, TLR7 and TLR8 in the lesions of CA were significantly higher than that in cervix scrape cells of HPV negative chronic cervicitis. There were no significant differences of TLR4 and TLR9 mRNA levels between the two groups. Conclusion There were higher expressions of some TLRs (3, 7, 8) and lower expression of TLR9 in the lesions of CA. Compared with HPV negative chronic cervicitis, the expressions of TLR1-3, TLR5-8, TLR10 mRNA in the lesions of CA were up-regulated. The expression profile of TLRs in different type of HPV infected CA lesions had no significant differences. Our results suggested that the expression profile of TLRs in CA may be associated with the HPV infection. Whether it was associated with the immune escape mechanism and persistent infection of HPV need further demonstration.

Association between angiotensin converting enzyme gene polymorphism and cerebral infarction / 中国康复理论与实践

@#ObjectiveTo explore the association between angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) polymorphism and cerebral infarction among Chinese people. MethodsThe ACE gene polymorphism was determined by PCR-RFLP in 242 patients with cerebral infarction and 283 controls. Multiple logistic regression was performed to explore the risk factors for cerebral infarction. ResultsAfter adjusting age, gender, alcohol drinking, smoking, education,history of diabetes mellitus and the primary hypertension, there was no significant association between ACE I/D polymorphism and cerebral infarction, either was hypertension and diabetes mellitus. The primary hypertension significanlly increased risk of cerebral infarction (OR=7.28,P =0.000). Both ACE ID/DD genotype and the primary hypertension showed a significant gene-environment interaction(r=1.62,OR=7.29), something as super multiplicative type 2 interaction. ConclusionAlthough ACE gene polymorphism is not risk factors of cerebral infarction, but ID/DD genotype had shown significant gene-environment interaction with primary hypertension in occurrence of cerebral infarcion.

Diagnostic performance of 64-channel multislice computed tomography in assessment of significant coronary artery disease in subjects suspected as acute coronary syndrome and stable angina / 北京大学学报(医学版)

Objective:To evaluate the diagnostic accuracy of 64-channel multislice spiral computed tomography(MSCT) in subjects with presentations suggestive of stable angina or acute coronary syndrome. Methods: Subjects received both 64-channel MSCT and coronary angiography, from Feb. 2006 to Feb. 2007, were enrolled for retrospective analyses. Results of the quantitative coronary angiography were used as the "Golden criteria", accuracy of 64-channel MSCT were evaluated in the overall sample, as well as in subjects suspected of stable angina and acute coronary syndrome. Results: A total of 120 subjects were enrolled in the analyses. On the patient level, the sensitivity, specificity, and accuracy of 64-channel MSCT in detecting significant stenoses were 92.5%, 50%, and 87.5%, respectively. The overall ROC area under curve was 0.71. On the artery level, sensitivity, specificity, positive predictive value, negative predictive value, and ROC area under curve of 64-channel MSCT were 69.9%, 83.8%, 81.1%, 73.7%, and 0.77, respectively. Further analyses showed the sensitivity, specificity, positive predictive value, negative predictive value, and ROC area under curve of 64-channel MSCT in subjects presenting as stable angina and in subjects presenting as acute coronary syndrome were as follows: 70.2% vs 69.2%, 76.2% vs 86.0%, 74.7% vs 85.6%, 71.9% vs 69.9%, and 0.73 vs 0.78. Conclusion: The accuracy rates of 64-chanel MSCT in subjects presenting as stable angina and in subjects presenting as acute coronary syndrome were similar.

Gene Polymorphism to the Effects of Low Level Aromatic Solvents Exposure on Spontaneous Abortion / 环境与健康杂志

Objective To investigate the association between genetic polymorphisms of cytochrome P450 MSP1 gene and the glutathione s-transferase GSTM1 gene in female workers exposed to aromatic solvents and spontaneous abortion. Methods A retrospective epidemiological investigation was carried out among 276 female workers including 58 female workers with history of spontaneous abortion and 218 female workers without spontaneous abortion selected in Yanshan of Beijing by the trained investigators using the unified questionnaire. Results The spontaneous abortion of female workers was significantly associated with GSTM1 (absent) (OR=2.07, 95% CI: 1.15-3.71), but not MSP1 (present) and exposure to aromatic solvent. After adust-ment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stress, the multiple logistic regression analysis showed that GSTM1 gene (absent) significantly increased the risk of spontaneous abortion of female workers (OR=2.15, 95% CI: 1.17-3.98). Before and after adjustment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stess, the multiple regression analysis showed that GSTM1 (absent) combined with MSP1 (heterozygous variant type / homozygous variant type) significantly increased the risk of spontaneous abortion (OR=2.98, 95% CI:l. 17-7.59), using the group with GSTM1 (present) and MSP1 (homozygous wild type) as reference group. Conclusion Our data suggested a genetic influence on spontaneous abortion in this population, GSTM1 (absent) was significantly associaled with spontaneous abortion, also provide evidence of additional joint action of gene MSP1 (heterozygous variant type and homozygous variant type) and GSTM1 (absent) to spontaneous abortion.