A randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease.

Exercise and diet are treatments for nonalcoholic fatty liver disease (NAFLD) and prediabetes, however, how exercise and diet interventions impact gut microbiota in patients is incompletely understood. We previously reported a 8.6-month, four-arm (Aerobic exercise, n = 29; Diet, n = 28; Aerobic exercise + Diet, n = 29; No intervention, n = 29) randomized, singe blinded (for researchers), and controlled intervention in patients with NAFLD and prediabetes to assess the effect of interventions on the primary outcomes of liver fat content and glucose metabolism. Here we report the third primary outcome of the trial-gut microbiota composition-in participants who completed the trial (22 in Aerobic exercise, 22 in Diet, 23 in Aerobic exercise + Diet, 18 in No Intervention). We show that combined aerobic exercise and diet intervention are associated with diversified and stabilized keystone taxa, while exercise and diet interventions alone increase network connectivity and robustness between taxa. No adverse effects were observed with the interventions. In addition, in exploratory ad-hoc analyses we find that not all subjects responded to the intervention in a similar manner, when using differentially altered gut microbe amplicon sequence variants abundance to classify the responders and low/non-responders. A personalized gut microbial network at baseline could predict the individual responses in liver fat to exercise intervention. Our findings suggest an avenue for developing personalized intervention strategies for treatment of NAFLD based on host-gut microbiome ecosystem interactions, however, future studies with large sample size are needed to validate these discoveries. The Trial Registration Number is ISRCTN 42622771.

The Abuse Characteristics of Amphetamine-Type Stimulants in Patients Receiving Methadone Maintenance Treatment and Buprenorphine Maintenance Treatment.

OBJECTIVE: The purpose of this study was to retrospectively investigate the abuse characteristics of amphetamine-type stimulants (ATS) in patients receiving methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT). METHODS: A total of 58 MMT and 51 BMT patients abusing ATS were recruited from the drug maintenance treatment clinic of Ningbo Addiction Research and Treatment Center from January 2018 to December 2019. They were assessed using the amphetamine abuse questionnaire (AAQ), addiction severity index (ASI) and Barratt impulsiveness scale (BIS). Moreover, 40 MMT control patients, 40 BMT control patients and 20 healthy controls were also assessed using the BIS. All information was collected using the amphetamine abuse questionnaire (AAQ), Chinese version of addiction severity index (ASI-C) and Chinese version of Barratt impulsiveness scale (BIS-C) conducted by qualified psychologists. RESULTS: The interval of amphetamine use in the MMT group was shorter than the BMT group (P < 0.05). The drug use subscale score of ASI was higher in the MMT group than the BMT group (P < 0.05). The respective and total scores of attentional impulsiveness, motor impulsiveness and non-planning impulsiveness in BIS in the MMT group were all higher than the MMT control group (P < 0.05). The scores of motor impulsiveness and non-planning impulsiveness in the BMT group were higher than the BMT control group (P < 0.05). The respective and total scores in BIS in the MMT control group and the BMT control group were all higher than those in the healthy controls. CONCLUSION: The patients showing amphetamine abuse in maintenance therapy had a greater impulsiveness than those having other simple maintenance treatments, and patients under MMT may be more addicted to amphetamines in comparison with those having BMT.

"Turning Point": Evaluating the Impact of a Three-Month UK-Based Clinical Education Training Programme for Physicians from a Chinese Medical School.

PURPOSE: Transnational faculty development programmes are increasingly popular in medicine, although evaluation of such activities rarely consider longer-term outcomes or the impact of language training. This study attempts to fill this gap by evaluating the lasting impacts of a three-month clinical education and English language training programme at University College London Medical School, UK, for medical educators from Ningbo University, China. METHODS: In-depth, semi-structured interviews were conducted in China with 41 participants who had completed the programme between 2013 and 2018. Interview data were analysed using an inductive thematic analysis, and themes were categorised using the four primary components of the faculty development model outlined by Irby and O'Sullivan (2011) - context, facilitator, programme, and participant. RESULTS: Contextual impacts included the importance of participants learning in the familiar environment of their own clinical discipline, the cultural enrichment gained by spending time overseas, reflecting on differences in health-care systems, and attempts to implement and disseminate learning on return to China. Facilitator-related factors included new insights into the student-educator relationship and valuing the support of programme mentors. Programme-related factors included exposure to new teaching methods and technical presentation skills, the challenges of navigating observership placements, spoken English language and pronunciation issues, and establishing a peer network of medical educators. Participant-related factors included improved confidence and self-reflection, adjusting educational approaches for different student groups, and career development in medical education. CONCLUSION: Participants gained teaching confidence from their engagement in the programme and many described it as a turning point in their careers as educators. Although in the period after attending, individuals changed their own practices and influenced colleagues within their organisation, often through taking on senior roles, systematic education changes were generally not implemented. Dedicated English language classes and clinical placements were considered the most positive features of the programme.

"Doctor, teacher, translator:" International medical students' experiences of clinical teaching on an English language undergraduate medical course in China.

Background: Like many Chinese universities, Ningbo University (NBU) has two undergraduate medical courses - one taught in Mandarin for domestic students, and one taught in English for international students. This study examines the experiences of medical students who recently completed the English language program that has a particular focus on clinical placements. Methods: In-depth, face-to-face, semi-structured interviews were conducted with 10 final year medical students at NBU in April 2019. Transcripts were analyzed using inductive thematic analysis. Results: All medical student participants were non native English speakers and had a limited grasp of Chinese. Their clinical teachers were all fluent in Chinese and had variable command of English. The large majority of patients in the teaching hospitals where placements took place spoke only in Chinese. Despite the obvious challenges arising from this, students still had predominantly positive experiences of clinical placements. Although students recognized that their clinical teachers' English proficiency was variable, they felt that other attributes, such as enthusiasm, interactivity, and a desire to teach were more important factors to their learning experiences. Discussion: Despite challenging linguistic circumstances, non native English-speaking students were able to navigate the challenges of studying clinical medicine from teachers with limited English language skills and with patients who spoke virtually no English. Further studies should explore the perceptions of teachers of the program, and graduate outcomes when these students enter the workplace. Educators involved in supporting international medical students should note that non technical curricular areas such as professionalism may require greater attention where language barriers exist.

Does sex hormone-binding globulin cause insulin resistance during pubertal growth?

BACKGROUND: The directional influences between serum sex hormone-binding globulin (SHBG), adiposity and insulin resistance during pubertal growth remain unclear. The aim of this study was to investigate bidirectional associations between SHBG and insulin resistance (HOMA-IR) and adiposity from childhood to early adulthood. METHODS: Participants were 396 healthy girls measured at baseline (age 11.2 years) and at 1, 2, 4 and 7.5 years. Serum concentrations of estradiol, testosterone and SHBG were determined by ELISA, glucose and insulin by enzymatic photometry, insulin-like growth factor 1 (IGF-1) by time-resolved fluoroimmunoassays, whole-body fat mass by dual-energy X-ray absorptiometry and HOMA-IR were determined by homeostatic model assessment. The associations were examined using cross-lagged path models. RESULTS: In a cross-lagged path model, SHBG predicted HOMA-IR before menarche ß = -0.320 (95% CI: -0.552 to -0.089), P = 0.007, independent of adiposity and IGF-1. After menarche, no directional effect was found between SHBG and insulin resistance or adiposity. CONCLUSIONS: Our results suggest that in early puberty, decline in SHBG predicts development of insulin resistance, independent of adiposity. However, after menarche, no directional influences between SHBG, adiposity and insulin resistance were found, suggesting that observational associations between SHBG, adiposity and insulin resistance in pubertal children may be subject to confounding. Further research is needed to understand the underlying mechanisms of the associations between SHBG and cardiometabolic risk markers in peripubertal children.

SSeCKS promoted lipopolysaccharide-sensitized astrocytes migration via increasing ß-1,4-galactosyltransferase-I activity.

Astrocytes migration is essential in the formation of the glial scar during the injury response process of the central nervous system (CNS) especially during inflammation. Integrin ß1 is part of the extracellular matrix receptors in the CNS and it has been reported that integrin ß-deficient astrocytes randomly migrate into wounds. Previous studies have found that ß-1,4 Galactosyltransferase-I (ß-1,4-GalT-I) enhanced the ß-1,4-galactosylation of integrin ß1. Src-suppressed C kinase substrate (SSeCKS) is an inflammatory response protein which functionally interacts with ß-1,4 Galactosyltransferase-I (ß-1,4-GalT-I). In this study we aim to investigate the role of SSeCKS and ß-1,4-GalT-I in the migration of astrocytes during lipopolysaccharide (LPS)-induced inflammation. Coimmunoprecipitation and immunofluorescence assays have demonstrated that SSeCKS and ß-1,4-GalT-I were significantly enhanced in LPS-treated astrocytes and their interactions may occur in the Trans-Golgi Network. Lectin blot showed that the knockdown of ß-1,4-GalT-I could inhibit the ß-1,4-galactosylation of glycoproteins including integrin ß1 with and without LPS, and that SSeCKS knockdown inhibits the ß-1,4-galactosylation of glycoproteins including integrin ß1 only in LPS-induced astrocytes. Additionally, wound healing assays indicated that ß-1,4-GalT-I knockdown could inhibit astrocytes migration with and without LPS but SSeCKS inhibited cell migration only when LPS was present. Therefore our findings suggest that SSeCKS affects astrocytes migration by regulating the ß-1,4-galactosylation of glycoproteins including integrin ß1, via ß-1,4-GalT-I expression in LPS-sensitized astrocytes.

Risk of second primary cancers in women diagnosed with endometrial cancer in German and Swedish cancer registries.

Along with the increasing incidence and favorable prognosis, more women diagnosed with endometrial cancer may develop second primary cancers (SPCs). We aimed at investigating risk of SPCs after endometrial cancer in Germany and Sweden to provide insight into prevention strategies for SPCs. Endometrial cancer patients diagnosed at age ≥15 years in Germany during 1997-2011 and in Sweden nationwide during 1997-2012 were selected. Standardized incidence ratios (SIRs), calculated as the ratio of observed to expected numbers of cases, were used to assess the risk of a specific second cancer after endometrial cancer for both German and Swedish datasets. Among 46,929 endometrial cancer survivors in Germany and 18,646 in Sweden, overall 2,897 and 1,706 SPCs were recorded, respectively. Significantly elevated SIRs were observed in Germany for ovarian (SIR = 1.3; 95%CI:1.1-1.5) and kidney cancers [1.6 (1.3-1.8)], while in Sweden the SIRs were 5.4 (4.6-6.3) and1.4 (1.0-1.9), respectively. Elevated risk for second ovarian endometrioid carcinoma was pronounced after early (<55 years) onset endometrial cancer in Germany [9.0 (4.8-15)] and Sweden [7.7 (5.1-11)]. In Germany elevated risks were found for second ovarian endometrioid carcinoma after endometrioid histology of first endometrial cancer [6.3 (4.0-9.4)] and for second kidney cancer after clear cell histology of endometrial cancer [4.9 (1.6-11)]. We found exceptionally elevated risk of second ovarian endometrioid carcinoma after endometrial cancer of the same histology or of early onset. Risk for second kidney cancer was also increased, particularly after endometrial cancer of clear cell histology. Cancer prevention strategies should focus on these cancers after endometrial cancer diagnosis.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot. RESULTS: Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all). CONCLUSIONS: Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

Association of four CpG-SNPs in the vascular-related genes with coronary heart disease.

Vascular-related gene polymorphism can affect the susceptibility of coronary heart disease. In current study, we aimed to evaluate the contribution of four vascular-related gene CpG-SNPs to coronary heart disease (CHD). A total of 784 angiography-proven CHD patients and 746 non-CHD controls were included in the current association study. The four CpG-SNPs (including VEGFA rs1005230, ACE rs4316, CST3 rs3827143 and AGTR1 rs275653) were genotyped using the Sequenom MassARRAY platform. All genotype distribution of four SNPs met HWE. Among the four CpG-SNPs, none was found to be associated with CHD on both genotype and allele levels. Further subgroup tests by age or gender were unable to observe any significant associations of them with CHD. Our case-control study showed that none of four CpG-SNPs in the vascular-related genes was associated with the risk of CHD in Han Chinese, although we could not exclude other genetic variants of these vascular-related genes with contribution to CHD.

Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1ß (IL-1ß2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1ß mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.

Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males.

BACKGROUND: The GCK gene encodes hexokinase 4, which catalyzes the first step in most glucose metabolism pathways. The purpose of our study is to assess the contribution of GCK methylation to type 2 diabetes (T2D). METHODS AND RESULTS: GCK methylation was evaluated in 48 T2D cases and 48 age- and gender-matched controls using the bisulphite pyrosequencing technology. Among the four CpG sites in the methylation assay, CpG4 and the other three CpGs (CpG1-3) were not in high correlation (r<0.5). Significantly elevated methylation levels of GCK CpG4 methylation were observed in T2D patients than in the healthy controls (P=0.004). A breakdown analysis by gender indicated that the association between CpG4 methylation and T2D was specific to males (P=0.002). It is intriguing that another significant male-specific association was also found between GCK CpG4 methylation and total cholesterol (TC) concentration (r=0.304, P=0.036). CONCLUSION: Our results showed that elevated GCK CpG4 methylation might suggest a risk of T2D in Chinese males. Gender disparity in GCK CpG4 methylation might provide a clue to elaborate the pathogenesis of T2D.

BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males.

BCL11A is a critical modulator involved in hemoglobin switching. Recent studies have established an association between BCL11A gene polymorphisms and a risk of type 2 diabetes (T2D). The aim of the present study was to assess the correlation between BCL11A DNA methylation and T2D. A total of 48 T2D cases and 48 age- and gender-matched controls were recruited to evaluate BCL11A methylation using bisulfite pyrosequencing technology. Although no significant association was observed in BCL11A methylation between T2D patients and healthy controls (P=0.322), breakdown analysis by gender identified a significant association between BCL11A methylation and T2D in males (P=0.018). Notably, there was also a significant female-specific association between the mean BCL11A DNA methylation and triglyceride (TG) concentration (r=-0.34; P=0.019). The results indicated that BCL11A methylation contributed to the risk of T2D in males. In addition, BCL11A methylation may have an effect on the development of T2D by influencing TG metabolism. Thus, gender difference may provide new information to aid the understanding of T2D pathogenesis.

Investigation into the promoter DNA methylation of three genes (CAMK1D, CRY2 and CALM2) in the peripheral blood of patients with type 2 diabetes.

Promoter DNA methylation may reflect the interaction between genetic backgrounds and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). Calcium/calmodulin-dependent protein kinase 1D (CAMK1D), cryptochrome 2 (CRY2) and calmodulin 2 (CALM2) genes have been identified to be associated with a risk of T2D. Therefore, the aim of the present study was to investigate the contribution of promoter DNA methylation of these genes to the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of the CpG dinucleotides within the CAMK1D, CRY2 and CALM2 gene promoters were measured in 48 patients with T2D and 48 age- and gender-matched healthy controls. The results demonstrated that the promoters of these three genes were hypomethylated in the peripheral blood of all the subjects, and DNA methylation of these three genes did not contribute to the risk of T2D.

Significant association between TAP2 polymorphisms and rheumatoid arthritis: a meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a severe chronic immune mediated inflammatory disease that has been shown to be associated with human leukocyte antigen (HLA) loci. The transporter associated with antigen processing 2 (TAP2) has been identified to play an important role in the HLA-associated diseases and immune response. The goal of our meta-analysis was to summarize the contribution of TAP2 polymorphisms to the risk of RA. METHODS: Meta-analyses were performed between RA and 3 TAP2 coding polymorphisms that comprised TAP2-379Ile > Val (rs1800454), TAP2-565Ala > Thr (rs2228396) and TAP2-665Thr > Ala (rs241447). The meta-analyses were involved with 9 studies (24 individual studies) among 973 cases and 965 controls. RESULTS: Meta-analyses showed that TAP2-379Ile allele was significantly associated with an increased risk of RA (p = 0.0002, odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.18-1.74). This association was further shown only in the dominant model (p = 0.006, OR = 1.59, 95% CI = 1.14-2.22). Subgroup analyses by ethnicity revealed that the association of TAP2-379Ile was significant in Asians (p = 0.03, OR = 1.38, 95% CI = 1.04-1.83). In addition, another significant association of TAP2-565Thr allele with RA was observed in Europeans (p = 0.002, OR = 1.62, 95% CI = 1.20-2.20). CONCLUSIONS: Our meta-analyses suggested that TAP2-379Ile allele was significantly associated with a 59% increased risk in the dominant effect model. Subgroup analyses by ethnicity showed that TAP2-379-Ile increased the risk of RA by 38% in Asians and TAP2-565Thr increased the risk of RA by 38% in Europeans. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2097080313124700.

Meta-analysis of low density lipoprotein receptor (LDLR) rs2228671 polymorphism and coronary heart disease.

Low density lipoprotein receptor (LDLR) can regulate cholesterol metabolism by removing the excess low density lipoprotein cholesterol (LDL-C) in blood. Since cholesterol metabolism is often disrupted in coronary heart disease (CHD), LDLR as a candidate gene of CHD has been intensively studied. The goal of our study is to evaluate the overall contribution of LDLR rs2228671 polymorphism to the risk of CHD by combining the genotyping data from multiple case-control studies. Our meta-analysis is involved with 8 case-control studies among 7588 cases and 9711 controls to test the association between LDLR rs2228671 polymorphism and CHD. In addition, we performed a case-control study of LDLR rs2228671 polymorphism with the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T allele was significantly associated with a reduced risk of CHD (P = 0.0005, odds ratio (OR) = 0.83, and 95% confidence interval (95% CI) = 0.75-0.92). However, rs2228671-T allele frequency was rare (1%) and was not associated with CHD in Han Chinese (P = 0.49), suggesting an ethnic difference of LDLR rs2228671 polymorphism. Meta-analysis has established rs2228671 as a protective factor of CHD in Europeans. The lack of association in Chinese reflects an ethnic difference of this genetic variant between Chinese and European populations.

GCK gene-body hypomethylation is associated with the risk of coronary heart disease.

OBJECTIVES: Glucokinase encoded by GCK is a key enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Variants of GCK gene were shown to be associated with type 2 diabetes (T2D) and coronary heart disease (CHD). The goal of this study was to investigate the contribution of GCK gene-body methylation to the risk of CHD. DESIGN AND METHODS: 36 patients (18 males and 18 females) and 36 age- and sex-matched controls were collected for the current methylation research. DNA methylation level of the CpG island (CGI) region on the GCK gene-body was measured through the sodium bisulfite DNA conversion and pyrosequencing technology. RESULTS: Our results indicated that CHD cases have a much lower methylation level (49.77 ± 6.43%) compared with controls (54.47 ± 7.65%, P = 0.018). In addition, GCK gene-body methylation was found to be positively associated with aging in controls (r = 0.443, P = 0.010). CONCLUSIONS: Our study indicated that the hypomethylation of GCK gene-body was significantly associated with the risk of CHD. Aging correlates with an elevation of GCK methylation in healthy controls.

Male-specific association between dopamine receptor D4 gene methylation and schizophrenia.

OBJECTIVE: The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ. METHODS: Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls. RESULTS: Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation. CONCLUSION: The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ.

Polymorphisms of DRD2 and DRD3 genes and Parkinson's disease: A meta-analysis.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects ~2% of the population aged ≥65 years. The degeneration of dopamine neurons in the substantia nigra contributes to the pathogenesis of PD. Dopamine receptor D2 (DRD2) and dopamine receptor D3 (DRD3) are two key subtypes of dopamine receptors. The aim of our study was to evaluate the association between the polymorphisms of DRD2 and DRD3 genes and PD. Meta-analyses were conducted from 16 studies (46 stages) among 4,279 cases and 5,661 controls between PD and 9 polymorphisms (DRD2: rs1800497, rs1079597, rs6278, rs6279, rs273482, rs1799732 and rs1076563; DRD3: rs6280 and rs2134655). A significant association was observed between DRD3 rs2134655 polymorphism and PD [P=0.01, odds ratio (OR)=1.17, 95% confidence interval (CI): 1.03-1.32] and a borderline association was observed between DRD2 rs1800497 polymorphism and PD in Europeans (P=0.05, OR=1.13, 95% CI: 1.00-1.27). Findings of the current meta-analysis suggested that DRD3 rs2134655 polymorphism was associated with a 17% increased risk of PD and that DRD2 rs1800497 polymorphism had a potential to increase the risk of PD by 13% in Europeans. Future large-scale studies are required to confirm the ethnic difference of DRD2 rs1800497 polymorphism and to determine whether there were significant associations of PD with other polymorphisms in DRD2 and DRD3 genes.

Meta-analyses between 18 candidate genetic markers and overweight/obesity.

AIMS: The goal of our study is to investigate the associations between 18 candidate genetic markers and overweight/obesity. METHODS: A total of 72 eligible articles were retrieved from literature databases including PubMed, Embase, SpingerLink, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang. Meta-analyses of 18 genetic markers among 56,738 controls and 48,148 overweight/obese persons were done by Review Manager 5.0. RESULTS: Our results showed that SH2B1 rs7498665 polymorphism was significantly associated with the risk of overweight/obesity (overall odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.09-1.34, P = 0.0004). Increased risk of overweight/obesity was also observed in FAIM2 rs7138803 polymorphism (overall OR = 1.11, 95% CI = 1.01-1.22, P = 0.04). CONCLUSION: Our meta-analyses have shown the important role of 2 polymorphisms (SH2B1 rs7498665 and FAIM2 rs7138803) in the development of overweight/obesity. This study highlighted the importance of above two candidate genes (SH2B1 and FAIM2) in the risk of overweight/obesity. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2785487401176182.