Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms

The activation of the ATP-gated P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7) produces microglial activation, a process which has been demonstrated in depression, bipolar disorder, and schizophrenia. Emerging data over the last years highlighted the importance of P2X7 cation channel as a potential drug target for these central nervous system disorders. The Gln460Arg (rs2230912) polymorphism of the P2RX7 gene has been widely studied in mood disorders, however the results are still controversial. Therefore, we aimed to investigate the C-terminal region of this gene in major depressive and bipolar disorders (MDD and BD) by studying possibly functional, non-synonymous polymorphisms within a 7 kb long region around the Gln460Arg, including Ala348Thr (rs1718119), Thr357Ser (rs2230911), and Glu496Ala (rs3751143) variants. Since Gln460Arg is located at the 3' end of the P2RX7 gene, we included additional, potentially functional single nucleotide polymorphisms (SNPs) from the 3' untranslated region (UTR), which can be in linkage with Gln460Arg. Based on in silico search, we chose two SNPs in putative microRNA target sites which are located in consecutive positions: rs1653625 and rs1718106.P2RX7 SNPs from the C-terminal region were selected based on previous functional assays, 3' UTR variants were chosen using PolymiRTS and Patrocles databases. The genotyping of the non-synonymous SNPs was carried out by pre-designed TaqMan® kits, while the 3' UTR variants were analyzed by PCR-RFLP method. Case-control analyses were carried out between 315 inpatients with acute major depressive episode (195 MDD, 120 BD) and 406 healthy control subjects. The two subscales of the Hospital Anxiety and Depression Scale (HADS) self-report questionnaire were used for quantitative analyses, including an additional, "at-risk" population of 218 patients with diabetes mellitus. The in vitro reporter gene assays were carried out on HEK and SK-N-FI cells transiently transfected with pMIR vector constructs containing the P2RX7 3' UTR downstream of the luciferase gene.Haplotype analysis indicated a relatively high linkage between the analyzed P2RX7 SNPs. Our case-control study did not yield any association between P2RX7 gene variants and depression. However, dimensional analyses showed significant associations of the HADS depression severity scores with Gln460Arg (rs2230912) and Ala348Thr (rs1718119) in the depressed and diabetic patient groups. In the in vitro experiments, the P2RX7 3' UTR constructs with the lowest predicted binding efficiency to their miRNAs showed the highest expression of the gene. The combination of the depression-associated P2RX7 C-terminal and 3' UTR SNPs contributed to the highest depression severity score in the haplotype analysis. Based on our findings, we propose that a P2RX7 haplotype combination of the Gln460Arg and neighboring SNPs contribute to the observed genetic association with depressive symptoms

Rapporteur summaries of plenary, symposia, and oral sessions from the XXIIIrd World Congress of Psychiatric Genetics Meeting in Toronto, Canada, 16-20 October 2015

The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the International Society of Psychiatric Genetics, was held in Toronto, ON, Canada, on 16-20 October 2015. Approximately 700 participants attended to discuss the latest state-of-the-art findings in this rapidly advancing and evolving field. The following report was written by trainee travel awardees. Each was assigned one session as a rapporteur. This manuscript represents the highlights and topics that were covered in the plenary sessions, symposia, and oral sessions during the conference, and contains major notable and new findings. © 2016 Wolters Kluwer Health, Inc

It Is High Time for Personalized Dietary Counseling in Celiac Disease: A Systematic Review and Meta-Analysis on Body Composition

The body composition of patients with celiac disease (CD), on which the effects of a gluten-free diet (GFD) are controversial, differs from that of the average population. In this study, we aimed to compare the body composition across CD patients before a GFD, CD patients after a one-year GFD and non-celiac control subjects. A systematic search was conducted using five electronic databases up to 15 July 2021 for studies that reported at least one of the pre-specified outcomes. In meta-analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. A total of 25 studies were eligible for systematic review, seven of which were included in meta-analysis. During a ≥1-year GFD, fat mass of CD patients, compared to that at baseline, significantly increased (WMD = 4.1 kg, 95% CI = 1.5 to 6.6, three studies). In CD patients after a ≥1-year GFD, compared to non-celiac controls, fat mass (WMD = −5.8 kg, 95% CI = −8.7 to −2.9, three studies) and fat-free mass (WMD = −1.9 kg, 95% CI = −3.0 to −0.7, three studies) were significantly lower. In conclusion, body composition-related parameters of CD patients differ from that of the non-celiac control subjects even after a longstanding GFD

Cardiovascular risk factors in coeliac disease (ARCTIC): a protocol of multicentre series of studies

Introduction There is only limited and controversial information available on the cardiovascular (CV) risk in coeliac disease (CD). In this study, we plan to investigate the body composition and CV risk-related metabolic parameters at the diagnosis of CD and on a gluten-free diet in a Hungarian cohort of patients with CD.Methods and analysis This study consists of two case–control studies and a prospective cohort study, involving newly diagnosed and treated patients with CD with age and sex-matched non-CD control subjects with an allocation ratio of 1:1. CD-related symptoms, quality of life, quality of the diet and CV risk will be assessed with questionnaires. Our primary outcomes are body composition parameters, which will be estimated with InBody 770 device. Secondary outcomes are CV-risk related metabolic parameters (eg, serum lipids, haemoglobin A1c, homeostatic model assessment index, liver enzymes, homocysteine, interleukin 6, galectin-3) and enteral hormones (leptin, ghrelin, adiponectin) measured from venous blood samples for all participants. Fatty liver disease will be assessed by transabdominal ultrasonography. In statistical analysis, descriptive and comparative statistics will be performed. With this study, we aim to draw attention to the often neglected metabolic and CV aspect of the management of CD. Findings may help to identify parameters to be optimised and reassessed during follow-up in patients with CD.Ethics and dissemination The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals.Trial registration number NCT05530070