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Aims: This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta® in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues. Methods: A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16 weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of − 0.35% (− 3.83 mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > − 0.35% (− 3.83 mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53 mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated. Results: After 16 weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of − 1.10% ± 1.31% (− 12.0 mmol/mol ± 14.3 mmol/mol) in the generic exenatide group and − 1.08% ± 1.11% (− 11.8 mmol/mol ± 12.1 mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was − 0.03% (− 0.33 mmol/mol), with a lower one-sided 95% CI limit of − 0.27% (− 2.95 mmol/mol), which was higher than the prespecified non-inferiority margin of − 0.35% (− 3.83 mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53 mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05). Conclusions: In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16 weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015. [ABSTRACT FROM AUTHOR]

The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120–1.892), dominant genetic model (OR 1.266, 95% CI 1.027–1.546), and recessive genetic model (OR 1.306, 95% CI 1.040–1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 μmol/L), least abundant in CC genotype (11.37 ± 5.23 μmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 μmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135–1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population. [ABSTRACT FROM AUTHOR]

• The association of CD33 single nucleotide polymorphisms and PD susceptibility was verified in the northern Chinese Han population. • Polymorphisms in CD33 rs12985029 and rs3826656 are linked to PD. • The rs3826656 GA genotype may have a protective effect on PD, while the A allele of rs12985029 may increase the PD incidence. Parkinson's disease (PD) represents the multisystem illness involving immunological and neuroinflammatory dysfunction. The present work focused on evaluating link of CD33 single nucleotide polymorphisms (SNPs) with PD vulnerability of the northern Chinese Han people, considering CD33's role as a critical immunoregulatory receptor in neuroinflammatory responses. The present case-control study included 475 PD cases together with 475 normal controls. A further division of PD patients into two categories was made: 74 patients with early-onset PD (EOPD; onset age ≤ 50 years) and 401 patients with late-onset PD (LOPD; onset age > 50 years). DNA extraction was conducted, followed by genotyping for 2SNPs of CD33 polymorphisms with polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). Alleles (G vs. A, P = 0.028) and AA genotypes (P = 0.042) of rs12985029 were significantly different between the groups. Distinctions were observed between the two groups in the recessive, co-dominant, and additive models (nominal P = 0.030, nominal P = 0.045, and P = 0.032). AA genotype frequency among male PD was higher compared to corresponding male controls (P = 0.034), and in the male group allele A was a factor causing the disease (P = 0.026). The rs12985029 genotypes and allele frequency were different in EOPD compared with LOPD (P = 0.002, P = 0.002, respectively), and in LOPD group relative to healthy control group (P = 0.020 and P = 0.004, separately). Regarding the rs3826656 polymorphism, the frequency of GA genotype was higher in the control group than in the case group (nominal P = 0.036). Overdominance and co-dominant models were different between these groups (P = 0.026, nominal P = 0.030). Subgroup analysis revealed genotype frequency differences between rs3826656 LOPD group and control group (P = 0.018). Furthermore, relationship between rs3826656 and rs12985029 (D' = 0.162, r2 = 0.021) did not reach a complete level of linkage disequilibrium (LD) of northern Chinese Han people. This study establishes an association between CD33 rs12985029 and rs3826656 polymorphisms and PD risk among the selected northern Chinese Han people. The GA genotype, rs3826656, may act as a protective factor against PD, while the A allele, rs12985029,could be genetic risk factor related to PD. Future research should include larger sample sizes and other human populations to further investigate how CD33 polymorphisms contribute to PD. [ABSTRACT FROM AUTHOR]

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The genetic basis of KBD remains elusive now. To investigate the relationship between PPARGC1B gene polymorphism and KBD, we conducted a two-stage association study using 2743 unrelated Han Chinese subjects. In the first stage, three SNPs rs1078324, rs4705372, and rs11743128 of PPARGC1B gene were genotyped in 559 KBD patients and 467 health controls using Sequenom MassARRAY platform. In the second stage, the association analysis results of PPARGC1B with KBD were replicated using an independent sample of 1717 subjects. SNP association analysis was conducted by PLINK software. Genotype imputation was conducted by IMPUTE 2.0 against the reference panel of the 1000 genome project. Bonferroni multiple testing correction was performed. We observed a significant association signal at rs4705372 ( P = 0.0160) and a suggestive association signal at rs11743128 ( P = 0.0290). Further replication study confirmed the association signals of rs4705372 ( P = 0.0026) and rs11743128 ( P = 0.0387) in the independent validation sample. Our study results suggest that PPARGC1B is a novel susceptibility gene of KBD. [ABSTRACT FROM AUTHOR]

DDR2 gene, playing an essential role in regulating osteoblast differentiation and chondrocyte maturation, may influence bone mineral density (BMD) and osteoporosis, but the genetic variations actually leading to the association remain to be elucidated. Therefore, the aim of this study was to investigate whether the genetic variants in DDR2 are associated with BMD and fracture risk. This study was performed in three samples from two ethnicities, including 1,300 Chinese Han subjects, 700 Chinese Han subjects (350 with osteoporotic hip fractures and 350 healthy controls) and 2,286 US white subjects. Twenty-eight SNPs in DDR2 were genotyped and tested for associations with hip BMD and fractures. We identified 3 SNPs in DDR2 significantly associated with hip BMD in the Chinese population after multiple testing adjustments, which were rs7521233 (P = 1.06×10−4, β: −0.018 for allele C), rs7553831 (P = 1.30×10−4, β: −0.018 for allele T), and rs6697469 (P = 1.59×10−3, β: −0.015 for allele C), separately. These three SNPs were in high linkage disequilibrium. Haplotype analyses detected two significantly associated haplotypes, including one haplotype in block 2 (P = 9.54×10−4, β: −0.016) where these three SNPs located. SNP rs6697469 was also associated with hip fractures (P = 0.043, OR: 1.42) in the Chinese population. The effect on fracture risk was consistent with its association with lower BMD. However, in the white population, we didn’t observe significant associations with hip BMD. eQTL analyses revealed that SNPs associated with BMD also affected DDR2 mRNA expression levels in Chinese. Our findings, together with the prior biological evidence, suggest that DDR2 could be a new candidate for osteoporosis in Chinese population. Our results also reveal an ethnic difference, which highlights the need for further genetic studies in each ethnic group. [ABSTRACT FROM AUTHOR]

Kashin-Beck disease (KBD) is a chronic osteochondropathy. In this study, we conducted the first genome-wide copy number variation study (GCNVS) of KBD totally involving 2,743 Chinese Han adults. GCNVS was first performed using Affymetrix Human SNP6.0 Arrays. The identified copy number variations (CNVs) were then replicated in an independent Chinese Han sample containing 1,026 subjects. SNP genotyping, CNV identification and quality control were implemented by Birdsuite. STRUCTURE and EIGENSTRAT were applied for controlling potential population stratification in the GCNVS. Association analysis was conducted using PLINK. Microarray and qRT-PCR were also conducted to compare the expression levels of the genes overlapping with identified CNVs between KBD patients and healthy controls. GCNVS found that CNV452 ( P value = 7.78 × 10) overlapping with ABI3BP gene was significantly associated with KBD. Replication association study observed that rs9850273 ( P value = 0.008) and rs7613610 ( P value = 0.021) in ABI3BP gene were significantly associated with KBD. Gene expression analysis also found that ABI3BP was up-regulated in KBD patients compared to healthy controls. Our results suggest that ABI3BP was a novel susceptibility gene for KBD. [ABSTRACT FROM AUTHOR]

Background and Aims: The accuracy of glycosylated hemoglobin (HBA1c) detection for the diagnosis of gestational diabetes mellitus (GDM) has been extensively studied in the Chinese population, but the exact role of these detections remains controversial. The present meta-analysis was performed to establish the overall accuracy of HBA1c for the diagnosis of Chinese patients with GDM. Methods: After a systematic review of related studies, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and other measures about the accuracy of HBA1c in the diagnosis of GDM were pooled using random-effects models. The summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Results: Forty-one studies included 2812 Chinese patients with GDM and 5918 controls were included in our meta-analysis. The summary estimates for HBA1c in the diagnosis of GDM in the studies included were as follows: sensitivity 0.762 (95% confidence interval [CI]: 0.746-0.777), specificity 0.917 (95% CI: 0.910-0.924), PLR 8.21 (95% CI: 3.77-17.89), NLR 0.20 (95% CI: 0.09-0.44), and DOR 41.40 (95% CI: 11.47-149.38). Our data showed that the SROC curve is positioned near the desirable upper left corner of the SROC curve, while the area under curve (AUC) was 0.93 with a Q* value of 0.865. Conclusions: Measurement of HBA1c is likely to be a useful diagnostic tool for confirming GDM. The results of HBA1c should be interpreted in parallel with clinical findings and the results of conventional tests. [ABSTRACT FROM AUTHOR]

• NEK1 gene polymorphisms may be associated with sporadic Parkinson's disease in the Chinese Northern Han population. • NEK1 rs66509122 T allele may be a protective factor for Parkinson's disease. • The rs4563461 C allele was significantly associated with sleep disorders in Parkinson's disease. • The rs66509122 C allele was associated with diabetes in female patients and depression in the early-onset of Parkinson's disease. Parkinson's disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer's disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population. A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations. Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group. This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of obesity in Chinese adults increased from 1991 to 2000; however, recent changes in this trend are unclear. This study aims to estimate the current prevalence of obesity and to assess trends in obesity and BMI distribution in Chinese adults from 1991 through 2011.Methods: Height and weight measurements of 12,249 Chinese adults from the 2011 China Health and Nutrition Survey were analyzed (in 2013) together with China Health and Nutrition Survey data for 1991-2009. Obesity was defined as BMI≥28.0 kg/m(2) based on the Working Group on Obesity in China criteria.Results: In the 2011 survey, the age-adjusted mean BMI was 23.8 (95% CI=23.7, 23.9) for men and 23.4 (95% CI=23.2, 23.5) for women. The age-adjusted prevalence of obesity was 11.3% (95% CI=10.8%, 11.9%) overall, 11.8% (95% CI=10.8%, 12.6%) among men, and 11.0% (95% CI=10.3%, 11.8%) among women. Estimates of age-adjusted obesity prevalence among the Chinese population were significantly lower than those of the U.S. population (all p<0.05). Over the 20-year period, the prevalence of obesity increased from 2.88% to 11.8% among men (age-adjusted annual change in OR=1.08, 95% CI=1.07, 1.09, p<0.001) and from 4.55% to 11.0% among women (OR=1.05, 95% CI=1.05, 1.06, p<0.001). Similar significant findings were observed for both men and women based on WHO recommendations.Conclusions: The prevalence of obesity among both Chinese men and women increased significantly from 1991 through 2011, particularly among men. [ABSTRACT FROM AUTHOR]

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of KBD remains unknown. To identify relevant biological pathways for KBD, we conducted a genome-wide pathway-based association study (GWPAS) following by replication analysis, totally using 2743 Chinese Han adults. A modified gene set enrichment algorithm was used to detect association between KBD and 963 biological pathways. Cartilage gene expression analysis and serum complement measurement were performed to evaluate the functional relevance of identified pathway with KBD. We found that the Complement and Coagulation Cascades (CACC) pathway was significantly associated with KBD ( P value = 3.09 × 10 − 5 , false-discovery rate = 0.042). Within the CACC pathway, the most significant association was observed at rs1656966 ( P value = 1.97 × 10 − 4 ) of KNG1 gene. Further replication study observed that rs1656966 ( P value = 0.037) was significantly associated with KBD in an independent validation sample of 1026 subjects. Gene expression analysis observed that CFD (ratio = 3.39 ± 2.68), A2M (ratio = 3.67 ± 5.63), C5 (ratio = 2.65 ± 2.52) and CD46 (ratio = 2.29 ± 137) genes of the CACC pathway were up-regulated in KBD articular cartilage compared to healthy articular cartilage. The serum level of complement C5 in KBD patients were significantly higher than that in healthy controls ( P value = 0.038). Our study is the first to suggest that complement system-related CACC pathway contributed to the development of KBD. [ABSTRACT FROM AUTHOR]

Personal care products, such as additives, have raised widespread concerns about the potential threat to male reproductive health. The spermatogenesis in humans lasts for approximately 90 days, the average levels of these chemicals remain unclear during spermatogenesis. In our study, we pooled urine samples from each man during the days of 1–15, 16–31, 32–63, and ≥64, and examined exposure to 48 typical additive chemicals. By principal component analysis (PCA), k-means clustering, and Spearman's rank correlations, we then identified 6 PC scores and 4 clusters based on profiles of these chemicals. Some industrial, commercial or structural similar chemicals (e.g., phthalates) were significantly correlated compared to unrelated chemicals (e.g., benzophenone). PCA scores were associated with individual lifestyles (e.g., household income, tea consumption, and drinking tap water). Distinct exposure components and exposure patterns of personal care products may help the reproductive health assessment of men. We suggested more concerns for widespread exposure to these chemicals for men. [Display omitted] • Typical additive chemicals are exposed to men of reproductive age. • Six PC scores and four clusters were characterized profiles of cumulative chemical exposure. • Exposure patterns of chemicals may help the reproductive health assessment of adult men. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Hip fractures (HF) are a major cause of public health burden with strong genetic determination. However, the true causal genes remain largely unknown. Materials and methods: Based on the important biological role of estrogens in bone homeostasis, this study aimed to investigate whether the estrogen receptor genes, ESR1 and ESR2, affect the onset of HF in 700 elderly Chinese subjects (350 with osteoporotic HF and 350 healthy controls). We genotyped 32 SNPs in total and examined their associations both by the single-SNP and haplotype tests. Results: We identified two novel SNPs of ESR1, rs3020314 and rs1884051, were significantly associated with HF (rs3020314: P =0.0004, OR=1.66, 95%CI: 1.25–2.18; rs1884051: P =0.0004, OR=1.46, 95%CI: 1.19–1.81). We firstly detected significant association of ESR2 with HF (rs960070: P =0.0070, OR=1.43, 95%CI: 1.10–1.86). Haplotype analyses corroborated our single-SNP results. Conclusion: Our findings have important implications for understanding the pathology of osteoporotic fractures. Independent replication studies are needed to validate our results and explore the most possible functional variants for molecular studies. [Copyright &y& Elsevier]