Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Evaluation of Acarbose Bioequivalence in Healthy Chinese Populations Using Novel Pharmacodynamic End Points.

Acarbose is a widely used α-glucosidase inhibitor for the management of postprandial hyperglycemia in patients with type 2 diabetes mellitus. Recent pilot studies on acarbose bioequivalence (BE) have successfully identified additional pharmacodynamic (PD) parameters as valid end points. Nevertheless, there was a scarcity of published pivotal studies using novel PD parameters. The purpose of the study is to investigate the acarbose BE using the new PD parameters. The study was conducted with an open, randomized, 2-period crossover design. A total of 64 healthy Chinese volunteers received either the reference (R) or test (T) acarbose at a dose of 2×50 mg orally, followed by a 1-week washout period. After sucrose treatment (baseline) and sucrose/acarbose co-administration, serum glucose, and insulin concentrations were assessed. The rectifying approach yielded geometric mean ratios of 102.9% for maximum serum glucose concentration with deduction of glucose concentration at 0 hour and 105.3% for the area under the serum glucose concentration-time curve profile 0-2 hours after coadministration of sucrose and acarbose with deduction of baseline (AUC0-2 h,r ). The 90% confidence intervals of maximum serum glucose concentration with deduction of glucose concentration at 0 hour and the area under the serum glucose concentration-time curve profile 0-2 hours after coadministration of sucrose and acarbose with deduction of baseline all fell within the acceptance limits. The incidence of adverse events after the T or R drug was comparable, and healthy subjects were well tolerated. The findings of our investigation clearly show that the PD parameters of the rectifying method exhibit enhanced suitability and sensitivity when assessing acarbose BE in healthy participants. The T and R drugs were bioequivalent using the novel PD parameters, and both drugs demonstrated good safety and tolerability.

Corrigendum: Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.

[This corrects the article DOI: 10.3389/fphar.2023.1169103.].

Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.

Objective: The main purpose of this study was to evaluate the pharmacokinetics, bioequivalence, and safety properties between a new generic and a brand reference formulation of esomeprazole enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions. Methods: The fasting study was an open-label, randomized, two-period crossover study conducted in 32 healthy Chinese volunteers, and the fed study was a four-period crossover study conducted in 40 healthy Chinese volunteers. Blood samples were collected at the specified time points and determined to obtain the plasma concentrations of esomeprazole. The primary pharmacokinetic parameters were calculated using the non-compartment method. Bioequivalence was analyzed by the geometric mean ratios (GMRs) of the two formulations and the corresponding 90% confidence intervals (CIs). The safety of the two formulations was assessed. Results: The fasting and fed study showed that the pharmacokinetics of the two formulations was similar. Under the fasting condition, the 90% CIs of GMRs of the test-to-reference formulation were 87.92%-104.36% for Cmax, 87.82%-101.45% for AUC0-t, and 87.99%-101.54% for AUC0-∞; under the fed condition, the 90% CIs of GMRs of the test-to-reference formulation were 80.53%-94.95% for Cmax, 87.46%-97.26% for AUC0-t, and 87.46%-97.16% for AUC0-∞. The 90% CIs of GMRs fall within the bioequivalence range of 80.00%-125.00%. The two formulations had good safety and were well-tolerated, and no serious adverse events occurred. Conclusion: According to relevant regulatory standards, esomeprazole enteric-coated generic and reference products exhibited bioequivalence and good safety in healthy Chinese subjects. Clinical Trials Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171347 and CTR20171484.

Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET® XR in healthy volunteers under fasting and fed conditions.

Background and Objectives: Janumet® XR is the combination of sitagliptin and extended metformin hydrochloride produced by Merck Sharp & Dohme. It is specially designed for diabetes mellitus patients taking both drugs already. Janumet® XR exhibited clinically significant blood glucose lowering efficacy and long-term use safety. However, no generic form of Janumet® XR has been approved in western countries. The relatively high cost made the medication less prescribed. A more affordable form of this drug may benefit an immense diabetes mellitus population. The current study compared the bioequivalence (BE) of sitagliptin 100 mg and metformin 1000 mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company to Janumet® XR in healthy Chinese subjects. Methods: Twenty-eight healthy Chinese subjects were enrolled in Study 1 and 2, respectively. Both studies were conducted with an open, randomized, two-period crossover design using the test (T) or the reference (R) drug. Study 1 is conducted under the fasting state, and Study 2 is under the fed state. Subjects received an oral dose of sitagliptin 100 mg and metformin 1000 mg, and plasma concentrations of sitagliptin and metformin were determined up to 72 h post-dose. Pharmacokinetic (PK) parameters, including maximum serum concentration (Cmax) and area under the concentration-time curve up to the last quantifiable concentration (AUC0-t) of both sitagliptin and metformin, were calculated and compared between the T and R treatments. Results: In the fasting study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 109.42%, 101.93%, and 101.95%, respectively; the corresponding ratios for metformin were 98.69%, 94.12%, and 93.42%, respectively. In the fed study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 98.41%, 100.30%, and 100.24%, respectively; the corresponding ratios for metformin were 97.79%, 99.28%, and 100.69%, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ in both studies were all within acceptance limits (80.00%-125.00%). Conclusion: The results demonstrated for the first time that sitagliptin 100 mg and metformin 1000 mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company was bioequivalent to the branded Janumet® XR, and both drugs were well tolerated.

The effect of food on the pharmacokinetics of WXFL10203614, a potential selective JAK1 inhibitor, in healthy Chinese subjects.

Objective: This study was performed to investigate the effect of food on the pharmacokinetics (PK) of WXFL10203614 in healthy Chinese subjects. Methods: This was a randomized, open-label, single-dose, two-treatment (fed vs fasted), two-period, two-sequence, crossover study. 14 eligible subjects were averagely randomized into 2 sequences and then received 10 mg WXFL10203614 under fasted or fed condition. In each period, the blood samples were collected from 0 h (pre-dose) and serially up to 72 h post-dose, and plasma concentrations were detected using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The effect of food on the PK profile and safety of WXFL10203614 were assessed. Results: 70 subjects were screened, and 14 subjects (10 male and 4 female) were enrolled and completed the study. Under the fasted condition, WXFL10203614 was absorbed rapidly with a Tmax of 0.98 h. The absorption rate was slower, Tmax delayed by 2.98 h, and the Cmax decreased by 16.3% when WXFL10203614 administered after the high-fat and high-calorie diet, other PK parameters were not affected. The 90% confidence intervals (CIs) for the ratio (fed/fasted) of geometric means of the Cmax, AUC0-t and AUC0-∞ were 0.73-1.01, 0.90-1.03 and 0.90-1.03, indicating that the high-fat and high-calorie diet might impact the absorption process of WXFL10203614. Although the Cmax was slightly decreased, there was no significant difference in the Cmax under fasted and fed conditions. Thus, it was not considered clinically significant owing to the small magnitude of changes in Cmax. All Treatment-emergent adverse events (TEAEs) were mild and resolved spontaneously without treatment. Conclusion: Food had no clinically relevant effects on drug system exposure of WXFL10203614. It was well tolerated under fasted and fed conditions in healthy Chinese subjects, so WXFL10203614 could be administered orally with or without food. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20191636.

Safety, tolerability and pharmacokinetics of WXFL10203614 in healthy Chinese subjects: A randomized, double-blind, placebo-controlled phase â study.

Objective: This study was conducted to investigate the safety, tolerability and pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in healthy Chinese subjects. Methods: A single-center, randomized, double-blind, placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In the single-dose study, Subjects were randomized into 7 dose levels of WXFL10203614 (1 mg group, n = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 8 subjects per group, 2 of them given placebo). In the multiple-dose study, subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 were all assessed. Results: A total of 592 subjects were screened, 50 subjects were enrolled in the single-dose study and 30 in the multiple-dose study. All adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was absorbed rapidly after dosing with Tmax of 0.48-0.98 h, Cmax, AUC0-t and AUC0-∞ were all increased in a dose-related manner over the range of 1-33 mg. Renal excretion was the major route of elimination of WXFL10203614. Steady-state PK parameters (Cmax,ss, AUC0-t,ss and AUC0-∞,ss) were elevated after once-daily administration of 5-10 mg WXFL10203614 and non- and weak drug accumulations were observed, whereas moderate drug accumulation occurred in the 5 mg BID group. Conclusion: WXFL10203614 exhibited good safety, tolerability and favorable PK profiles in healthy Chinese subjects, supporting further clinical development in patients with rheumatoid arthritis. Clinical Trials Registration Number: http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and CTR20200143.

Comparative Pharmacokinetics, Safety, and Immunogenicity Study of the Prefilled Syringe and Lyophilized Formulation of a Recombinant Human Tumor Necrosis Factor-α Receptor II:lgG Fc Fusion Protein in Healthy Chinese Male Subjects.

This study aimed to compare the pharmacokinetics, safety, and immunogenicity of the prefilled syringe (PFS) with lyophilized (LYO) recombinant human tumor necrosis factor-α receptor II:lgG Fc fusion protein (rhTNFR:Fc) in healthy Chinese male subjects. A single-center, randomized, open-label, 2-period, crossover study was performed in healthy Chinese male subjects. Subjects were randomly assigned into 2 sequences and received a subcutaneous injection of 25 mg rhTNFR:Fc PFS or rhTNFR:Fc LYO (Anbainuo), with a 35-day washout between the 2 periods. Blood samples were collected at specified time intervals, and then serum concentrations of rhTNFR:Fc were analyzed by enzyme-linked immunosorbent assay. The maximum serum concentration, area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all calculated and evaluated. Meanwhile, safety and immunogenicity were also assessed. A total of 82 subjects completed the study, and six subjects withdrew for various reasons. The 90%CIs for geometric mean ratios of maximum serum concentration, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all within the equivalence range of 80% to 125%. Safety was comparable between the 2 formulations with low immunogenicity. rhTNFR:Fc PFS exhibited similar pharmacokinetic and safety profiles of rhTNFR:Fc LYO (Anbainuo) in healthy Chinese male subjects.

A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects.

Objective: This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects. Methods: A single-center, randomized, double-blind, single-dose, parallel trial was performed in 84 Chinese healthy male subjects who randomly (1:1) received a single intravenous infusion of 1 mg/kg HOT-1010 or Avastin® for 90 min and followed up for 85 days. Serum concentrations of bevacizumab were analyzed by enzyme-linked immunosorbent assay. Primary pharmacokinetic parameters, Cmax, AUC0-t and AUC0-∞, were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed. Results: A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 91.81-103.64%, 85.19-95.39% and 85.04-95.36%, which were all within the bioequivalence margin. Treatment-emergent adverse events were reported in 27 (65.9%) subjects in HOT-1010 group and 23 (56.1%) subjects in Avastin® group. Most TEAEs were mild or moderate. No TEAEs, Serious Adverse Events or deaths leading to discontinuation was reported. Subjects were all tested negative for Anti-drug Antibody. Conclusion: HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, CTR20181610.

Identification of human uridine diphosphate-glucuronosyltransferase isoforms responsible for the glucuronidation of 10,11-dihydro-10-hydroxy-carbazepine.

OBJECTIVES: To determine the kinetics of the formation of 10,11-dihydro-10-hydroxy-carbazepine (MHD)-O-glucuronide in human liver microsomes (HLMs), human intestine microsomes (HIMs), human kidney microsomes (HKMs) and recombinant human UDP-glucuronosyltransferase (UGTs), and identify the primary UGT isoforms catalyzing the glucuronidation of MHD. METHODS: The kinetics of the glucuronidation of MHD was determined in HLMs, HIMs as well as HKMs. Screening assays with 13 recombinant human UGTs, inhibition studies and correlation analysis were performed to identify the main UGTs involved in the glucuronidation of MHD. KEY FINDINGS: MHD-O-glucuronide was formed in HLMs, HIMs as well as HKMs, HLMs showed the highest intrinsic clearance of MHD. Among 13 recombinant human UGTs, UGT2B7 and UGT1A9 were identified to be the principal UGT isoforms mediating the glucuronidation of MHD, while UGT1A4 played a partial role. In addition, inhibition studies and correlation analysis further confirmed that UGT2B7 and UGT1A9 participated in the formation of MHD-O-glucuronide. CONCLUSIONS: MHD could be metabolized by UGTs in the liver, intestine and kidney, and the hepatic glucuronidation was the critical metabolic pathway. UGT2B7 and UGT1A9 were the primary UGT isoforms mediating the formation of MHD-O-glucuronide in the liver.

Acarbose bioequivalence: Exploration of eligible protocol design.

WHAT IS KNOWN AND OBJECTIVE: Acarbose is a poorly absorbed α-glucosidase inhibitor that acts locally in the intestinal tract. Therefore, the evaluation of its bioequivalence (BE) should be based on pharmacodynamic (PD) rather than pharmacokinetic (PK) endpoints. Currently, there is no consensus on the best method for acarbose BE evaluation. The optimal protocol design regarding dosing time/dose and PD parameters requires further exploration. The aim of the study was to identify an optimum protocol for establishing acarbose BE in healthy Chinese volunteers using PD endpoints. METHODS: Three pilot studies were conducted in healthy Chinese subjects. Study 1 was an open, randomized, two-period crossover study using the reference (R) drug at the dose of 1 × 50 mg. Study 1 aimed to determine appropriate dosing time by comparing the PD effect of acarbose between two administration methods. One method was concomitant administration of sucrose and acarbose, and another method was acarbose administration 10 min before sucrose. Study 2 was an open, randomized, three-period crossover study. Subjects were given the R drug at the dose of 1 × 50 mg, 2 × 50 mg or 3 × 50 mg in a random sequence. The aim of Study 2 was to identify a reasonable dose of acarbose in the BE study. Study 3 was conducted with an open, randomized, three-period crossover design using the test (T) or R drug in an R-T-R sequence at the dose of 2 × 50 mg. Study 3 aimed to compare the BE between the R and T drug and determine intra-individual variation. Twelve subjects were recruited in Study 1, Study 2 and Study 3, respectively, with a one-week washout period. Serum glucose and insulin concentrations were determined after sucrose administration (baseline) and sucrose/acarbose co-administration. RESULTS AND DISCUSSION: In Study 1, no significant differences in PD parameters were found between the two administration methods. The results of Study 2 revealed that the optimal dose was between 1 × 50 mg and 2 × 50 mg. The comparison of PD parameters indicated that the rectifying method could distinguish between different formulations. Study 3 showed that the geometric mean ratios of Cmax, r , AUC0-2 h, r and AUC0-4 h, r were 90.06%, 84.55% and 84.21%, respectively, using the rectifying method. The 90% CIs of Cmax, r were within acceptance limits (80.00%-125.00%), whereas that of AUC0-2 h, r and AUC0-4 h, r were out of the range. The intra-individual variation was approximately 21% for R formulation. Based on the variation, the number of subjects needed to identify formulation differences in the pivotal study would be 55 with 90% power at the 5% level of significance. WHAT IS NEW AND CONCLUSION: The results from our study manifested that a randomized, balanced, two-way crossover design was eligible to evaluate acarbose BE. The appropriate dosing time was concomitant administration of sucrose and acarbose, and the optimal dose was 2 × 50 mg. The rectifying method exhibited preferable sensitivity and applicability in acarbose BE evaluation. A practical sample size of the pivotal study would be 55. These results may help to provide new insights into the protocol design of acarbose BE study.

The factors associated with geriatric depression in rural China: stratified by household structure.

Depressive symptoms and empty nest phenomenon of rural elderly people are both important public health issues, which should not be ignored. We aimed to estimate the prevalence of depressive symptoms and related factors of the empty nest elderly in rural China. We recruited 3182 eligible subjects and gathered data by face-to-face interview. Multivariate logistic regression models were used to explore the related factors of depressive symptoms. The present study showed that the prevalence of depressive symptoms significantly differed between empty nest old adults and non-empty nesters (24.1% vs. 19.0%). The elderly living alone had highest OR of depressive symptoms. Depressive symptoms of empty nest elderly was associated with sleep quality, economic status, pain, social support and ADL. While it was associated with gender, economic status, pain and PSMS in non-empty nest group. Number of chronic disease showed significant associations with depressive symptoms in the elderly living alone. Subjective support, support utilization and pain were positively associated with depressive symptoms in the elderly living with spouse. Sleep quality, economic status and ADL were common factors. Depressive symptoms obviously prevail among empty nest elderly than non-empty nesters. It reminded us that complementary social support from family and society is essential.

Associations of self-neglect with quality of life in older people in rural China: a cross-sectional study.

BACKGROUND: Elder self-neglect (ESN) has become a public health issue globally. Limited studies have focused on ESN, as well as the relationship between ESN and quality of life (QoL) in developing countries. The study's objective is to explore the association between ESN and QoL among rural elderly in China. METHODS: A cross-sectional study was conducted among 3,182 elder adults aged 60 years or older, using a cluster-sampling technique in one township in Dangtu, a county in Anhui province. All participants completed face-to-face interview in their household. QoL was assessed using a brief form of the World Health Organization's quality of life questionnaire (WHOQOL-BREF), and ESN was assessed using the Scale of the Elderly Self-neglect (SESN). Hierarchical linear regression models were used to analyze the associations between the ESN scores and QoL scores after adjusting for sociodemographic, social support, and physical and psychological variables. RESULTS: The scores of overall ESN and five domains were significantly correlated with the scores of four QoL domains (p < 0.001). After adjusting for sociodemographic characteristics, social support, and physical and psychological health characteristics, elders who reported higher overall self-neglect scores had significantly lower scores in the four QoL domains (p < 0.001). Education, economic level, physical health, ADL, depression, and cognitive function are consistent predictors across all QoL domains. CONCLUSIONS: ESN is an independent risk factor for poor QoL in elderly people in rural China. Understanding the role of ESN and its influence on QoL is important for the management of and intervention in ESN.

A prospective study of psychological resilience and depression among left-behind children in China.

This prospective study examined the longitudinal effects of psychological resilience on depression in a Chinese sample of left-behind children. A total of 386 left-behind children completed both a baseline and a 1-year follow-up survey. The prevalence of depression at the baseline and 1-year follow-up was 12.7 and 8.5 per cent, respectively. Multivariate analysis revealed that older age and baseline depressive symptoms were positively associated with follow-up depression, while psychological resilience and quality of life were negatively related to follow-up depression. Our findings provided preliminary evidence that higher psychological resilience was a significantly protective factor of developing depression among left-behind children.

Prevalence of Internet addiction and its association with social support and other related factors among adolescents in China.

A cross-sectional study design was applied amongst a random sample (n = 10158) of Chinese adolescents. Self-completed questionnaires, including demographic characteristics, Internet use situation, Youth Internet Addiction Test, Youth Social Support Rating Scale and Zung Self-rating Depression Scale were utilized to examine the study objectives. Among the study population, the prevalence rate of Internet addiction was 10.4%, with 1038 (10.2%) moderately and 21 (0.2%) severely addicted to the Internet. Results from the multivariate logistic regression analyses suggested that a variety of related factors have significant effects on Internet addiction (parental control, per capita annual household income, academic performance, the access to Internet, online activities). The correlation coefficients showed that Internet addiction was negatively correlated with social support and positively associated with depression. Social support had a significant negative predictive effect on Internet addiction. The mediating effect of depression between social support and Internet addiction was remarkable.

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.

Association between apolipoprotein E gene polymorphism and depression.

We performed an updated meta-analysis to obtain a more precise estimation of the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility to depression, as previous reports have been inconsistent. Twenty studies with 2286 depression patients and 3845 controls were included. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association between ApoE gene polymorphism and depression using a random effects model. Results showed a significant association between ApoE gene polymorphism and susceptibility to depression in the overall population (ε2/ε3 genotype versus ε3/ε3: OR 0.76, 95% CI 0.59-0.99). Subgroup analyses indicated an association in the Caucasian population (ε2 allele versus ε3: OR 0.75, 95% CI 0.58-0.97) as well as in late-life depression (LLD) patients (ε3/ε4 genotype versus ε3/ε3: OR 1.34, 95% CI 1.07-1.68, and ε4 allele versus ε3: OR 1.30, 95% CI 1.06-1.59). We concluded that the ε2/ε3 genotype likely provided a protective effect against depression in the overall population and the ε2 allele acted as a protective factor for depression in the Caucasian population while the ε4 allele and ε3/ε4 genotype were associated with an increased risk of depression in the LLD subjects.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.

Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95% CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95% CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis.

OBJECTIVE: Many studies have investigated the role of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T/A1298C polymorphisms in essential hypertension (EH), but results are inconclusive. The purpose of this meta-analysis was to clarify the effects of MTHFR C677T/A1298C polymorphisms on the risk of EH. METHODS: Electronic databases were searched to identify relevant studies published until January 2014. Data were extracted by two independent authors. Odds ratios (ORs) with 95%confidence intervals (CIs) were used to assess the association between MTHFR C677T/A1298C polymorphisms and the risk of EH using random effect models or fixed effect models. Finally,30 studies with 5207 cases and 5383 controls were included for C677T polymorphism and 6 studies with 1009 cases and 994 controls were included for A1298C polymorphism. RESULTS: Meta-analysis results indicated that MTHFR C677T polymorphism contributed to an increased risk of EH (for T vs. C: OR=1.30, 95%CI=1.18­1.43; for TT+CT vs. CC: OR=1.34, 95%CI=1.24­1.46; for TT vs. CC: OR=1.62, 95%CI=1.32­1.99; for TT vs. CT+CC: OR=1.41, 95%CI=1.26­1.59). However, no significant association was detected between MTHFR A1298C polymorphism and the risk of EH. CONCLUSION: This meta-analysis supports that MTHFR C677T polymorphism plays a role in developing EH. MTHFR A1298C polymorphism may not be associated with an increased risk of EH. Further large and well-designed studies are warranted to confirm these findings.

Association of microtubule associated protein tau/Saitohin (MAPT/STH) MAPT_238bp/STH Q7R polymorphisms and Parkinson's disease: A meta-analysis.

BACKGROUND: The association between the extended tau haplotype (H1) and susceptibility to Parkinson's disease (PD) was controversial in previous studies. Therefore, we performed this meta-analysis to determine whether the additional polymorphisms in MAPT_238bp and STH Q7R which both included in H1 are associated with PD. METHODS: 19 studies were identified by a search of PubMed, PDGENE, Elsevier, Springer Link, CBM (Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese), and Wanfang (Chinese) databases, up to May 2014. Additionally, manual retrieval of the references of identified articles was performed. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity. All the statistical tests were conducted using Stata 9.0. RESULTS: Both of MAPT_238bp/STH Q7R polymorphisms had a significant association with PD risk in all genetic models. Subgroup analyses by ethnicity showed that the association between MAPT_238bp polymorphism and PD existed in Caucasian populations. CONCLUSIONS: The results of this meta-analysis suggested that MAPT_238bp/STH Q7R polymorphisms might modulate the risk of PD susceptibility. Certainly, additional well-designed studies are required to confirm these findings.