دورية أكاديمية
Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1.
| العنوان: | Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1. |
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| المؤلفون: | Mühlhaus J; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Dinter J; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Jyrch S; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Teumer A; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Jacobi SF; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Homuth G; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, University of Greifswald, Greifswald, Germany., Kühnen P; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Wiegand S; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Grüters A; Department for Pediatric Endocrinology and Diabetology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany., Völzke H; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.; German Center for Diabetes Research (DZD), Greifswald, Germany., Raile K; Department for Pediatric Endocrinology and Diabetology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.; Experimental and Clinical Research Center (ECRC), Charité - Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine (HZ), Berlin, Germany., Kleinau G; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany.; Institut für Medizinische Physik und Biophysik, Group Protein X-ray Crystallography and Signal Transduction, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany., Krude H; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany., Biebermann H; Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universitt zu Berlin, Berlin, Germany. |
| المصدر: | Frontiers in pharmacology [Front Pharmacol] 2017 Nov 24; Vol. 8, pp. 807. Date of Electronic Publication: 2017 Nov 24 (Print Publication: 2017). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Media] |
| مستخلص: | Activation of trace amine-associated receptor 1 (TAAR1) in endocrine pancreas is involved in weight regulation and glucose homeostasis. The purpose of this study was the identification and characterization of potential TAAR1 variants in patients with overweight/obesity and disturbed glucose homeostasis. Screening for TAAR1 variants was performed in 314 obese or overweight patients with impaired insulin secretion. The detected variants were functionally characterized concerning TAAR1 cell surface expression and signaling properties and their allele frequencies were determined in the population-based Study of Health in Pomerania (SHIP). Three heterozygous carriers of the single nucleotide missense variants p.Arg23Cys (R23C, rs8192618), p.Ser49Leu (S49L, rs140960896), and p.Ille171Leu (I171L, rs200795344) were detected in the patient cohort. While p.Ser49Leu and p.Ille171Leu were found in obese/overweight patients with slightly impaired glucose homeostasis, p.Arg23Cys was identified in a patient with a complete loss of insulin production. Functional in vitro characterization revealed a like wild-type function for I171L, partial loss of function for S49L and a complete loss of function for R23C. The frequency of the R23C variant in 2018 non-diabetic control individuals aged 60 years and older in the general population-based SHIP cohort was lower than in the analyzed patient sample. Both variants are rare in the general population indicating a recent origin in the general gene pool and/or the consequence of pronounced purifying selection, in line with the obvious detrimental effect of the mutations. In conclusion, our study provides hints for the existence of naturally occurring TAAR1 variants with potential relevance for weight regulation and glucose homeostasis. |
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| فهرسة مساهمة: | Keywords: glucose homeostasis; signal transduction; trace amine-associated receptor 1; variants; weight regulation |
| تواريخ الأحداث: | Date Created: 20171212 Latest Revision: 20201001 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5705543 |
| DOI: | 10.3389/fphar.2017.00807 |
| PMID: | 29225575 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1663-9812 |
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| DOI: | 10.3389/fphar.2017.00807 |