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Xiaobin Zhang, Joanna Norton, Isabelle Carrière, Karen Ritchie, Isabelle Chaudieu, Joanne Ryan, Marie-Laure Ancelin
Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria...
February 15, 2017: Scientific Reports
Yoon Jin Choi, Nayoung Kim, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Jin-Wook Kim, Yong Sung Kim, Dong Ho Lee, Hyun Chae Jung
BACKGROUND AND AIM: Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD. METHODS: Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea...
February 4, 2017: Journal of Gastroenterology and Hepatology
A T Amare, K O Schubert, M Klingler-Hoffmann, S Cohen-Woods, B T Baune
Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders...
January 24, 2017: Translational Psychiatry
Sarah D Linnstaedt, Margaret G Walker, Kyle D Riker, Jennifer E Nyland, JunMei Hu, Catherine Rossi, Robert A Swor, Jeffrey S Jones, Luda Diatchenko, Andrey V Bortsov, David A Peak, Samuel A McLean
α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity...
February 2017: Pain
Csaba Vastagh, Annie Rodolosse, Norbert Solymosi, Zsolt Liposits
Gonadotropin-releasing hormone (GnRH) neurons play a key role in the central regulation of reproduction. In proestrous female mice, estradiol triggers the pre-ovulatory GnRH surge, however, its impact on the expression of neurotransmitter receptor genes in GnRH neurons has not been explored yet. We hypothesized that proestrus is accompanied by substantial changes in the expression profile of genes coding for neurotransmitter receptors in GnRH neurons. We compared the transcriptome of GnRH neurons obtained from intact, proestrous, and metestrous female GnRH-GFP transgenic mice, respectively...
2016: Frontiers in Cellular Neuroscience
Abhimanyu Garg, Shireesha Sankella, Chao Xing, Anil K Agarwal
Despite identification of causal genes for various lipodystrophy syndromes, the molecular basis of some peculiar lipodystrophies remains obscure. In an African-American pedigree with a novel autosomal dominant, atypical familial partial lipodystrophy (FPLD), we performed linkage analysis for candidate regions and whole-exome sequencing to identify the disease-causing mutation. Affected adults reported marked loss of fat from the extremities, with excess fat in the face and neck at age 13-15 years, and developed metabolic complications later...
June 16, 2016: JCI Insight
Alexis Michenet, Romain Saintilan, Eric Venot, Florence Phocas
BACKGROUND: In beef cattle, maternal care is critical for calf survival and growth. Our objective was to evaluate the major sources of additive genetic variation in maternal behavior and suckling performance in two genetically close beef breeds. METHODS: Maternal performance was assessed based on maternal behavior (MB), milk yield (MY) and udder swelling score (US) of 1236 Blonde d'Aquitaine cows and 1048 Limousin cows. MB was scored just after calving to describe the intensity of the dam's protective behavior towards her calf...
June 22, 2016: Genetics, Selection, Evolution: GSE
Geana Paula Kurita, Ola Ekholm, Stein Kaasa, Pål Klepstad, Frank Skorpen, Per Sjøgren
BACKGROUND AND PURPOSE: The effects of single-nucleotide polymorphisms (SNPs) on the cognitive function of opioid-treated patients with cancer until now have not been explored, but they could potentially be related to poor functioning. This study aimed at identifying associations between SNPs of candidate genes, high opioid dose, and cognitive dysfunction. METHODS: Cross-sectional multicenter study (European Pharmacogenetic Opioid Study, 2005-2008); 1586 patients; 113 SNPs from 41 genes...
July 2016: Brain and Behavior
Jian-Ping Zhang, Todd Lencz, Ryan X Zhang, Masahiro Nitta, Lawrence Maayan, Majnu John, Delbert G Robinson, W Wolfgang Fleischhacker, Rene S Kahn, Roel A Ophoff, John M Kane, Anil K Malhotra, Christoph U Correll
Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome)...
November 2016: Schizophrenia Bulletin
Vicneswari Shunmugam, Yee-How Say
BACKGROUND: α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. OBJECTIVES: This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population...
February 2016: Iranian Red Crescent Medical Journal
Abiodun Adefurin, Leon Darghosian, Chimalum Okafor, Vivian Kawai, Chun Li, Anushi Shah, Wei-Qi Wei, Daniel Kurnik, C Michael Stein
BACKGROUND: Acute myocardial infarction (AMI) is frequently associated with transient hyperglycemia even in patients without pre-existing diabetes. Acute stress can lead to increased blood glucose through the effect of catecholamines on alpha2A-adrenergic receptors (α2A-ARs) present in pancreatic islet β-cells. Variation in the gene (ADRA2A) that encodes the α2A-AR affects insulin release and glucose control and may play a particularly important role during times of stress. METHODS: We performed a retrospective cohort study using de-identified electronic medical records linked to a DNA repository in 521 Caucasians and 55 African-American non-diabetic patients with AMI...
July 15, 2016: International Journal of Cardiology
Rika Nishikawa, Hiroshi Nagai, Toshinori Bito, Tetsuya Ikeda, Tatsuya Horikawa, Atsuko Adachi, Tsukasa Matsubara, Chikako Nishigori
Anti-tumor necrosis factor (TNF)-α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome-wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti-TNF-α therapy using Human Omni Express-8 v1...
November 2016: Journal of Dermatology
Tor-Arne Hegvik, Kaya Kvarme Jacobsen, Mats Fredriksen, Tetyana Zayats, Jan Haavik
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood onset neuropsychiatric disorder with a complex and heterogeneous symptomatology. Persistence of ADHD symptoms into adulthood is common. Methylphenidate (MPH) is a widely prescribed stimulant compound that may be effective against ADHD symptoms in children and adults. However, MPH does not exert satisfactory effect in all patients. Several genetic variants have been proposed to predict either treatment response or adverse effects of stimulants...
August 2016: Journal of Neural Transmission
Zahra N Sohani, Sonia S Anand, Sebastien Robiou-du-Pont, Katherine M Morrison, Sarah D McDonald, Stephanie A Atkinson, Koon K Teo, David Meyre
BACKGROUND: Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood. OBJECTIVES: We investigate whether common genetic variants identified in adults have an effect on glucose in early life. METHODS: 610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied...
2016: PloS One
Elvira Ganic, Tania Singh, Cheng Luan, João Fadista, Jenny K Johansson, Holly Ann Cyphert, Hedvig Bennet, Petter Storm, Gaëlle Prost, Henrik Ahlenius, Erik Renström, Roland Stein, Leif Groop, Malin Fex, Isabella Artner
Monoamine and acetylcholine neurotransmitters from the autonomic nervous system (ANS) regulate insulin secretion in pancreatic islets. The molecular mechanisms controlling neurotransmitter signaling in islet β cells and their impact on diabetes development are only partially understood. Using a glucose-intolerant, MafA-deficient mouse model, we demonstrate that MAFA controls ANS-mediated insulin secretion by activating the transcription of nicotinic (ChrnB2 and ChrnB4) and adrenergic (Adra2A) receptor genes, which are integral parts of acetylcholine- and monoamine-signaling pathways...
March 1, 2016: Cell Reports
Luis A Tortajada-Genaro, Salvador Mena, Regina Niñoles, Marta Puigmule, Laia Viladevall, Ángel Maquieira
Pharmacological treatment of several diseases, such as attention-deficit hyperactivity disorder (ADHD), presents marked variability in efficiency and its adverse effects. The genotyping of specific single nucleotide polymorphisms (SNPs) can support the prediction of responses to drugs and the genetic risk of presenting comorbidities associated with ADHD. This study presents two rapid and affordable microarray-based strategies to discriminate three clinically important SNPs in genes ADRA2A, SL6CA2, and OPRM1 (rs1800544, rs5569, and rs1799971, respectively)...
March 2016: Analytical and Bioanalytical Chemistry
Marek Postula, Piotr K Janicki, Ceren Eyileten, Marek Rosiak, Agnieszka Kaplon-Cieslicka, Shigekazu Sugino, Radosław Wilimski, Dariusz A Kosior, Grzegorz Opolski, Krzysztof J Filipiak, Dagmara Mirowska-Guzel
The objective of this study was to investigate whether rare missense genetic variants in several genes related to platelet functions and acetylsalicylic acid (ASA) response are associated with the platelet reactivity in patients with diabetes type 2 (T2D) on ASA therapy. Fifty eight exons and corresponding introns of eight selected genes, including PTGS1, PTGS2, TXBAS1, PTGIS, ADRA2A, ADRA2B, TXBA2R, and P2RY1 were re-sequenced in 230 DNA samples from T2D patients by using a pooled PCR amplification and next-generation sequencing by Illumina HiSeq2000...
June 2016: Platelets
Batoul Kaabi, Ghania Belaaloui, Wassila Benbrahim, Kamel Hamizi, Mourad Sadelaoud, Wided Toumi, Hocine Bounecer
Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared...
April 2016: Pathology Oncology Research: POR
Michael M Havranek, Lea M Hulka, Eve Tasiudi, Christoph Eisenegger, Matthias Vonmoos, Katrin H Preller, Rainald Mössner, Markus R Baumgartner, Erich Seifritz, Edna Grünblatt, Boris B Quednow
Cocaine users characteristically display preferences for smaller immediate rewards over larger delayed rewards, and this delay discounting (DD) has been proposed as an endophenotype of cocaine addiction. Recent evidence suggests that the norepinephrine system and more specifically the α2A -adrenergic receptor (ADRA2A) are impacted by chronic cocaine use while also being potentially involved in the neural mechanisms underlying DD. Hence, we investigated the effects of ADRA2A polymorphisms and ADRA2A mRNA expression levels on DD of cocaine users and stimulant-naïve controls...
March 2017: Addiction Biology
Kazuo Hara, Takashi Kadowaki, Masato Odawara
INTRODUCTION: Type 2 diabetes (T2D) is a complex disease caused by an interaction between multiple genetic and environmental factors. T2D-associated loci identified by genome-wide association studies (GWAS) harbor the genes targeted by many clinically available drugs, supporting the idea that GWAS have the potential to discover novel genes for drug development. AREAS COVERED: This paper outlines, among the genes at those T2D-associated loci, the functional analysis of FTO, TCF7L2, SLC30A8, and MTNR1B, illustrating caveats we should be cautious about...
2016: Expert Opinion on Therapeutic Targets
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