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Genomics and Obesity

Maria Keller, Matthias Klös, Kerstin Rohde, Jacqueline Krüger, Tabea Kurze, Arne Dietrich, Michael R Schön, Daniel Gärtner, Tobias Lohmann, Miriam Dreßler, Michael Stumvoll, Matthias Blüher, Peter Kovacs, Yvonne Böttcher
DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan ( SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jennifer N Todd, Shylaja Srinivasan, Toni I Pollin
PURPOSE OF REVIEW: To provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D). RECENT FINDINGS: The prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth...
June 22, 2018: Current Diabetes Reports
D Gentilini, E Somigliana, L Pagliardini, E Rabellotti, P Garagnani, L Bernardinelli, E Papaleo, M Candiani, A M Di Blasio, P Viganò
Background: An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted...
2018: Clinical Epigenetics
Hyung Jun Woo, Jaques Reifman
BACKGROUND: Common metabolic diseases, including type 2 diabetes, coronary artery disease, and hypertension, arise from disruptions of the body's metabolic homeostasis, with relatively strong contributions from genetic risk factors and substantial comorbidity with obesity. Although genome-wide association studies have revealed many genomic loci robustly associated with these diseases, biological interpretation of such association is challenging because of the difficulty in mapping single-nucleotide polymorphisms (SNPs) onto the underlying causal genes and pathways...
June 20, 2018: BMC Medical Genomics
Xu Peng, Qiongyi Zhang, Cheng Liao, Weiping Han, Feng Xu
Obesity and its associated metabolic disorders are spreading at a fast pace throughout the world; thus, effective therapeutic approaches are necessary to combat this epidemic. Obesity develops when there is a greater caloric intake than energy expenditure. Promoting energy expenditure has recently attracted much attention as a promising approach for the management of body weight. Thermogenic adipocytes are capable of burning fat to dissipate chemical energy into heat, thereby enhancing energy expenditure. After the recent re-discovery of thermogenic adipocytes in adult humans, much effort has focused on understanding the molecular mechanisms, especially the epigenetic mechanisms, which regulate thermogenic adipocyte development and function...
June 17, 2018: International Journal of Molecular Sciences
Yahia A Kaabi
Context: Obesity is a major health concern in Saudi Arabia. Uncoupling protein 2 (UCP2) seems to play a major role in the regulation of human metabolism; therefore, genetic polymorphisms in the UCP2 gene might contribute to obesity. Aim: This study aims to establish whether 45-blood pressure (BP) insertion (I)/deletion (D) polymorphisms in UCP2 are associated with moderate and/or severe obesity in a Saudi Arabian population. Settings and Design: Case-control study design...
March 2018: Indian Journal of Endocrinology and Metabolism
Meena Balasubramanian, Diana S Johnson
BACKGROUND: Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes. OBJECTIVE: (s): To identify the underlying diagnosis in two families each with two siblings with variable level of ID through trio whole exome sequencing. METHODS: Both the families were recruited to the Deciphering Developmental Disorders (DDD) study to identify the aetiology for their ID...
June 13, 2018: European Journal of Medical Genetics
Yann C Klimentidis, David A Raichlen, Jennifer Bea, David O Garcia, Nathan E Wineinger, Lawrence J Mandarino, Gene E Alexander, Zhao Chen, Scott B Going
BACKGROUND/OBJECTIVES: Physical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual. SUBJECTS/METHODS: We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax  = 377,234) and two measures based on wrist-worn accelerometry data (nmax  = 91,084)...
June 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Erik Ingelsson, Mark I McCarthy
Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes through ever larger genome-wide association study meta-analyses...
June 2018: Circulation. Genomic and precision medicine
Sonia Roman
Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (< 200 IU/mL) in HBsAgnegative patients with or without serologic markers of previous viral exposure. The clinical significance of OBI is of concern in posttransfusional hepatitis B infection, hepatitis B reactivation, chronic liver disease and hepatocellular carcinoma (HCC). The diagnosis of OBI relays on the use of highly sensitive and specific laboratory techniques. Herein, comments derived from a study analyzing the frequency and characteristics of OBI in HCC Japanese patients are stated...
June 20, 2018: Annals of Hepatology
Heike Vogel, Anne Kamitz, Nicole Hallahan, Sandra Lebek, Tanja Schallschmidt, Wenke Jonas, Markus Jähnert, Pascal Gottmann, Lisa Zellner, Timo Kanzleiter, Mareike Damen, Delsi Altenhofen, Ralph Burkhardt, Simone Renner, Maik Dahlhoff, Eckhard Wolf, Timo D Müller, Matthias Blüher, Hans-Georg Joost, Alexandra Chadt, Hadi Al-Hasani, Annette Schürmann
To explore the genetic determinants of obesity and type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone NZO mouse strain with four different lean strains (B6, DBA, C3H, 129P2) which vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 QTL for obesity, 190 QTL for diabetes-related traits, and 100 QTL for plasma metabolites in the outcross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data...
June 8, 2018: Human Molecular Genetics
Juan Bai, Ying Zhu, Ying Dong
Obesity is known to induce pathological changes in the gut and diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology. The purposes of this study were to identify the effects of bitter melon powder (BMP) on the global gene expression pattern in the colon mucosa of obese rats. Obese rats were fed a high-fat diet and treated without or with BMP for 8 weeks. Genome-wide expression profiles of the colon mucosa were determined by RNA sequencing (RNA-Seq) analysis at the end of experiment...
June 2018: Genes & Genomics
Ying Sun, Jiao Fang, Yuhui Wan, Jingjing Hu, Yuanyuan Xu, Fangbiao Tao
OBJECTIVE: To examine whether polygenic susceptibility for body mass index (BMI) interacts with cumulative stress exposure, potentially exacerbating and buffering the effects of chronic stress, to predict obesity during childhood. METHODS: Data were analyzed from an established prospective puberty cohort in Anhui province, China. A total of 1000 children (421 boys and 579 girls, mean (standard deviation) age 8.97 (0.86) years) who had complete DNA genotyping, hair cortisol concentration and BMI were eligible for the study...
June 11, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Gönül Çatli, Haruki Fujisawa, Özgür Kırbıyık, Mizuho S Mimoto, Pinar Gencpinar, Taha Reşid Özdemir, Bumin Nuri Dündar, Alexandra M Dumitrescu
SECISBP2 is an essential factor in selenoprotein synthesis and its mutations result in a multiorgan syndrome including abnormal thyroid hormone metabolism. A ten-year-old obese Turkish boy born to consanguineous parents presented with high T4, low T3, high rT3 and normal or slightly elevated TSH. He also had attention deficit disorder and muscle weakness but no delay in growth or bone age. Sequencing of genomic DNA revealed a novel c.800_801insA, p.K267Kfs*2 mutation, homozygous in the proband and heterozygous in both parents and his brother...
June 8, 2018: Thyroid: Official Journal of the American Thyroid Association
S Pamela K Shiao, Haiyan Xiao, Lixin Dong, Xiaoling Wang, Kebin Liu, Jinxiong She, Huidong Shi
Despite evidences linking methylation changes in the cancer tissues, little is known about the methylation modification in the peripheral blood. With the current study, we identified differential methylation regions (DMRs) across human genome by collecting the blood samples of colorectal cancer (CRC) patients compared to that of their blood-related family who shared genetic inheritance and environmental influences, and unrelated obese and non-obese controls by accessing publicly available Gene Expression Omnibus data...
May 22, 2018: Oncotarget
Nicholas J Hudson, Marina Naval-Sánchez, Laercio Porto-Neto, Miguel Pérez-Enciso, Antonio Reverter
Asian and European wild boars were independently domesticated ca. 10,000 years ago. Since the 17th century, Chinese breeds have been imported to Europe to improve the genetics of European animals by introgression of favourable alleles, resulting in a complex mosaic of haplotypes. To interrogate the structure of these haplotypes further, we have run a new haplotype segregation analysis based on information theory, namely compression efficiency (CE). We applied the approach to sequence data from individuals from each phylogeographic region (n = 23 from Asia and Europe) including a number of major pig breeds...
June 5, 2018: Journal of Animal Science
Yili Wu, Haiping Duan, Xiaocao Tian, Chunsheng Xu, Weijing Wang, Wenjie Jiang, Zengchang Pang, Dongfeng Zhang, Qihua Tan
Previous genome-wide association studies on anthropometric measurements have identified more than 100 related loci, but only a small portion of heritability in obesity was explained. Here we present a bivariate twin study to look for the genetic variants associated with body mass index and waist-hip ratio, and to explore the obesity-related pathways in Northern Han Chinese. Cholesky decomposition model for 242 monozygotic and 140 dizygotic twin pairs indicated a moderate genetic correlation ( r = 0.53, 95%CI: 0...
2018: Frontiers in Genetics
Bassem M Shoucri, Victor T Hung, Raquel Chamorro-García, Toshi Shioda, Bruce Blumberg
Early life exposure to endocrine disrupting chemicals (EDCs) is an emerging risk factor for the development of obesity and diabetes later in life. We previously showed that prenatal exposure to the EDC tributyltin (TBT) results in increased adiposity in the offspring. These effects linger into adulthood and are propagated through successive generations. TBT activates two nuclear receptors, the peroxisome proliferator-activated receptor γ (PPARγ) and its heterodimeric partner retinoid X receptor (RXR), that promote adipogenesis in vivo and in vitro...
May 31, 2018: Endocrinology
Swapna Siddamalla, Tumu Venkat Reddy, Suresh Govatati, Praveen Guruvaiah, Mamata Deenadayal, Sisinthy Shivaji, Manjula Bhanoori
OBJECTIVE: Polycystic Ovary Syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder. In addition to hyperandrogenism, acne, hirsutism, obesity, oligoanovulation and infertility, insulin resistance is also a common feature in women of PCOS. Tumor suppressor genes (TSGs) perform essential function in the maintenance of genomic stability and regulatory pathways influencing the activity of several replication and transcription factors. The main aim of this study was to investigate the association of Single Nucleotide Polymorphisms of TP53, BRCA1and BRCA2 genes with the susceptibility to PCOS in South Indian women...
May 24, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Amadou H Togo, Awa Diop, Matthieu Million, Marie Maraninchi, Jean-Christophe Lagier, Catherine Robert, Fabrizio Di Pinto, Didier Raoult, Pierre-Edouard Fournier, Fadi Bittar
A novel strain of a Gram-stain negative, non-motile, non-spore forming rod-shaped, obligate anaerobic bacterium, designated AT11T , was isolated from a stool sample of a morbidly obese woman living in Marseille, France. This bacterium was characterized using biochemical, chemotaxonomic, and phylogenetic methods. The 16S rRNA gene sequence analysis showed that strain AT11T had a 97.8% nucleotide sequence similarity with Eisenbergiella tayi strain B086562T , the closest species with standing in nomenclature. The major cellular fatty acids of the novel isolate were C16:0 followed by saturated or unsaturated C18 fatty acids (C18:1 n9, C18:1 n5 and C18:0) ...
June 1, 2018: Current Microbiology
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