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https://www.readbyqxmd.com/read/27933546/using-systems-genetics-to-understanding-the-etiology-of-complex-disease
#1
Ramesh Ram, Grant Morahan
Here, we discuss Systems Genetics applications for systematic evaluation of candidate causal genes together with follow-up bioinformatics pathway analysis. The aim of this chapter is to illustrate analytic procedures and we provide examples in the context of Type 1 diabetes (T1day), the risk of which is conferred by over 60 loci. We also describe the Type 1 Diabetes Systems Genetics website and provide a guide for its use and application to other diseases.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933519/heterogeneous-stock-populations-for-analysis-of-complex-traits
#2
Leah C Solberg Woods, Richard Mott
Heterogeneous Stock (HS) populations allow for fine-resolution genetic mapping of a variety of complex traits. HS mice and rats were created from breeding together eight inbred strains, followed by maintaining the colony in a manner that minimizes inbreeding. After 50 or more generations of breeding, the resulting animals' chromosomes represent a genetic mosaic of the founders' haplotypes, with the average distance between recombination events in the centiMorgan range. This allows for genetic mapping to only a few Mb, a much smaller region than what can be identified using traditional F2 intercross or backcross mapping strategies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27932304/vitamin-d-and-type-2-diabetes
#3
REVIEW
Paul Lips, Marelise Eekhoff, Natasja Vzn Schoor, Mirjam Oosterwerff, Renate de Jongh, Yvonne Krul-Poel, Suat Simsek
Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes...
December 5, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27931609/clinical-and-biological-insights-into-combined-post-and-pre-capillary-pulmonary-hypertension
#4
Tufik R Assad, Anna R Hemnes, Emma K Larkin, Andrew M Glazer, Meng Xu, Quinn S Wells, Eric H Farber-Eger, Quanhu Sheng, Yu Shyr, Frank E Harrell, John H Newman, Evan L Brittain
BACKGROUND: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). OBJECTIVES: The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH...
December 13, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27931194/serum-albumin-to-globulin-ratio-is-related-to-cognitive-decline-via-reflection-of-homeostasis-a-nested-case-control-study
#5
Teruhide Koyama, Nagato Kuriyama, Etsuko Ozaki, Daisuke Matsui, Isao Watanabe, Fumitaro Miyatani, Masaki Kondo, Aiko Tamura, Takashi Kasai, Yoichi Ohshima, Tomokatsu Yoshida, Takahiko Tokuda, Ikuko Mizuta, Shigeto Mizuno, Kei Yamada, Kazuo Takeda, Sanae Matsumoto, Masanori Nakagawa, Toshiki Mizuno, Yoshiyuki Watanabe
BACKGROUND: Recent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD. METHODS: A total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD...
December 8, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27931122/modulation-of-pancreatic-islets-function-and-survival-during-aging-involves-the-differential-regulation-of-endoplasmic-reticulum-stress-by-p21-and-chop
#6
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios Papavassiliou, Hippokratis Kiaris
AIMS: While endoplasmic reticulum (ER) stress is recognized as a major mechanism causing pancreatic dysfunction in diabetes, little is known on how aging modulates the process. Here we compared the response to ER stress, viability and insulin release from pancreatic islets of young (6 weeks) or aged (14 months) mice. RESULTS: Islets from aged mice were more sensitive to ER stress than their younger counterparts, they exhibited more pronounced unfolded protein response (UPR) and caspase activation and displayed compromised insulin release after high glucose stimulation...
December 8, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27931035/diabetic-phenotype-in-the-small-intestine-of-zucker-diabetic-fatty-rats
#7
Henning Hvid, Stina Rikke Jensen, Brent M Witgen, Christian Fledelius, Jesper Damgaard, Charles Pyke, Thomas Bovbjerg Rasmussen
BACKGROUND/AIMS: In contrast to streptozotocin (STZ)-induced rodent models of diabetes, there are no thorough characterizations of the intestinal phenotype and the underlying changes in the global gene-expression of genetic models of diabetes, such as the Zucker diabetic fatty (ZDF) rat. The aim of the present study was to characterize the intestine in the ZDF rat. METHODS: The intestine of ZDF rats and lean controls was examined macroscopically and histologically, and ribonucleic acid sequencing (RNAseq) was performed in samples of jejunal mucosa...
December 9, 2016: Digestion
https://www.readbyqxmd.com/read/27930695/coordinated-activation-of-vegf-vegfr-2-and-ppar%C3%AE-pathways-by-a-multi-component-chinese-medicine-dhi-accelerated-recovery-from-peripheral-arterial-disease-in-type-2-diabetic-mice
#8
Shuang He, Tiechan Zhao, Hao Guo, Yanzhi Meng, Gangjian Qin, David A Goukassian, Jihong Han, Xuimei Gao, Yan Zhu
Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model...
2016: PloS One
https://www.readbyqxmd.com/read/27930580/association-of-rage-gene-gly82ser-polymorphism-with-coronary-artery-disease-and-ischemic-stroke-a-systematic-review-and-meta-analysis
#9
Wen-Qi Ma, Qing-Rong Qu, Yu Zhao, Nai-Feng Liu
BACKGROUND: The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and ischemic stroke (IS) remain controversial. The Gly82Ser polymorphism is located in the ligand-binding V domain of RAGE, suggesting a possible influence of this variant on RAGE function. The aim of the present study is to clarify the association between the RAGE Gly82Ser polymorphism and susceptibility to CAD and IS...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27929711/dual-effects-of-a-retn-single-nucleotide-polymorphism-snp-at-420-on-plasma-resistin-genotype-and-dna-methylation
#10
Hiroshi Onuma, Yasuharu Tabara, Ryoichi Kawamura, Jun Ohashi, Wataru Nishida, Yasunori Takata, Masaaki Ochi, Tatsuya Nishimiya, Yasumasa Ohyagi, Ryuichi Kawamoto, Katsuhiko Kohara, Tetsuro Miki, Haruhiko Osawa
CONTEXT: We previously reported that SNP (single nucleotide polymorphism) -420 C>G (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of CpG dinucleotides. OBJECTIVE: To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420. DESIGN AND METHODS: Genomic DNA was extracted from peripheral white blood cells in 2,078 Japanese subjects...
December 8, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27929430/biological-activities-of-extracts-from-loquat-eriobotrya-japonica-lindl-a-review
#11
REVIEW
Yilong Liu, Wenna Zhang, Changjie Xu, Xian Li
Loquat (Eriobotrya japonica Lindl.) is a subtropical fruit tree with high medicinal value native to China. Different organs of loquat have been used historically as folk medicines and this has been recorded in Chinese history for thousands of years. Research shows that loquat extracts contain many antioxidants, and different extracts exhibit bioactivity capable of counteracting inflammation, diabetes, cancer, bacterial infection, aging, pain, allergy and other health issues. Bioactive compounds such as phenolics and terpenoids have been isolated and characterized to provide a better understanding of the chemical mechanisms underlying the biological activities of loquat extracts...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27929407/polymorphism-of-the-transcription-factor-7-like-2-gene-tcf7l2-interacts-with-obesity-on-type-2-diabetes-in-the-predimed-study-emphasizing-the-heterogeneity-of-genetic-variants-in-type-2-diabetes-risk-prediction-time-for-obesity-specific-genetic-risk-scores
#12
Dolores Corella, Oscar Coltell, Jose V Sorlí, Ramón Estruch, Laura Quiles, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, Olga Castañer, Fernando Arós, Manuel Ortega-Calvo, Lluís Serra-Majem, Enrique Gómez-Gracia, Olga Portolés, Miquel Fiol, Javier Díez Espino, Josep Basora, Montserrat Fitó, Emilio Ros, José M Ordovás
Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample...
December 6, 2016: Nutrients
https://www.readbyqxmd.com/read/27929393/xylobiose-an-alternative-sweetener-ameliorates-diabetes-related-metabolic-changes-by-regulating-hepatic-lipogenesis-and-mir-122a-33a-in-db-db-mice
#13
Eunjin Lim, Ji Ye Lim, Eunju Kim, Yoo-Sun Kim, Jae-Ho Shin, Pu Reum Seok, Sangwon Jung, Sang-Ho Yoo, Yuri Kim
Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR...
December 5, 2016: Nutrients
https://www.readbyqxmd.com/read/27928437/increased-copeptin-levels-in-metabolic-syndrome-from-a-romanian-population
#14
Vintilă M, Gheorghiu Ml, Caragheorgheopol A, Baculescu N, Lichiardopol C, Badiu C, Coculescu M, Grigorescu F, Poiană C
Rationale: Arginine vasopressin (AVP) is secreted under conditions of water deprivation. Since AVP has a low half-life in the plasma, the C-terminal fragment of AVP-precursor (copeptin) was used to estimate the AVP levels. High copeptin levels increase the risk for the development of diabetes mellitus. Aim: This study was aimed to measure copeptin levels in the metabolic syndrome (MetS) in Romanians using a competitive enzyme immunoassay. Methods and results: Patients prone to present MetS (n = 63) were compared to controls (n = 42)...
October 2016: Journal of Medicine and Life
https://www.readbyqxmd.com/read/27928162/role-of-mirnas-in-the-pathogenesis-and-susceptibility-of-diabetes-mellitus
#15
REVIEW
Naoko Hashimoto, Tomoaki Tanaka
MicroRNAs (miRNAs) are noncoding RNAs of ~22 nucleotides that regulate gene expression post-transcriptionally by binding to the 3' untranslated region of messenger RNA (mRNAs), resulting in inhibition of translation or mRNA degradation. miRNAs have a key role in fine-tuning cellular functions such as proliferation, differentiation and apoptosis, and they are involved in carcinogenesis, glucose homeostasis, inflammation and other biological processes. In this review, we focus on the role of miRNAs in the pathophysiology of the metabolic disease and diabetes mellitus, the hallmark of which is hyperglycemia caused by defective insulin secretion and/or action...
December 8, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27927804/obstacles-to-translating-genotype-phenotype-correlates-in-metabolic-disease
#16
REVIEW
Anu Sharma, Adrian Vella
Type 2 diabetes mellitus is a polygenic disease with a variable phenotype. Many genetic associations have been described; however, understanding their underlying pathophysiological role in Type 2 diabetes mellitus is important for development of future therapeutic targets. Here, we review the physiological mechanisms of diabetes-associated variants that affect glycemia.
January 2017: Physiology
https://www.readbyqxmd.com/read/27926889/precision-medicine-diabetes-and-the-u-s-food-and-drug-administration
#17
Robert J Meyer
The U.S. Food and Drug Administration (FDA) has long sought to achieve the broader use of personalized medicine, which is better targeting of FDA-approved therapies through incorporating precise knowledge of a patient's underlying condition to therapies optimally chosen to match those needs. While some strides have been made in precision medicine-particularly in oncology and rare genetic diseases-most of the standard general medicine indications have yet to realize the benefits of precision-guided therapies...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27926811/p22phox-c242t-gene-polymorphism-and-overt-diabetic-nephropathy-a-meta-analysis-of-1-452-participants
#18
Yan-Yan Li, Ge Gong, Hong-Yu Geng, Yun Qian
Background/Aims: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. Methods: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model...
December 8, 2016: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/27922820/rapamycin-treatment-benefits-glucose-metabolism-in-mouse-models-of-type-2-diabetes
#19
Peter C Reifsnyder, Kevin Flurkey, Austen Te, David E Harrison
Numerous studies suggest that rapamycin treatment promotes insulin resistance, implying that rapamycin could have negative effects on patients with, or at risk for, type 2 diabetes (T2D). New evidence, however, indicates that rapamycin treatment produces some benefits to energy metabolism, even in the context of T2D. Here, we survey 5 mouse models of T2D (KK, KK-Ay, NONcNZO10, BKS-db/db, TALLYHO) to quantify effects of rapamycin on well-recognized markers of glucose homeostasis within a wide range of T2D environments...
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27921429/-congenital-hyperinsulinism-loss-of-b-cell-self-control
#20
Jan Lebl, Klára Roženková, Štěpánka Průhová
Congenital hyperinsulinism is a serious blood glucose regulation defect that interferes with brain development, leading to mental retardation, neurological sequelae and secondary epilepsy and ultimately may be life-threatening. Congenital hyperinsulinism (CHI) is caused by genetic defects of regulation of insulin secretion that induce insulin oversecretion in intrauterine life and postnatally. The clinical consequence is fetal macrosomia and subsequently neonatal and infantile hypoglycaemia. The most severe form is caused by biallelic mutations of KCNJ11 and ABCC8 genes that encode both potassium channel subunits, whereas their heterozygous mutations as well as enzymatic defects (GLUD1, HADH, GCK) lead to milder presentation...
2016: Vnitr̆ní Lékar̆ství
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