دورية أكاديمية

Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1

التفاصيل البيبلوغرافية
العنوان: Investigation of Naturally Occurring Single-Nucleotide Variants in Human TAAR1
المؤلفون: Jessica Mühlhaus, Juliane Dinter, Sabine Jyrch, Alexander Teumer, Simon F. Jacobi, Georg Homuth, Peter Kühnen, Susanna Wiegand, Annette Grüters, Henry Völzke, Klemens Raile, Gunnar Kleinau, Heiko Krude, Heike Biebermann
المصدر: Frontiers in Pharmacology, Vol 8 (2017)
بيانات النشر: Frontiers Media S.A., 2017.
سنة النشر: 2017
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: trace amine-associated receptor 1, variants, weight regulation, glucose homeostasis, signal transduction, Therapeutics. Pharmacology, RM1-950
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1663-9812
العلاقة: http://journal.frontiersin.org/article/10.3389/fphar.2017.00807/fullTest; https://doaj.org/toc/1663-9812Test
DOI: 10.3389/fphar.2017.00807
الوصول الحر: https://doaj.org/article/70f71652672f496dac3d4a66943fb522Test
رقم الانضمام: edsdoj.70f71652672f496dac3d4a66943fb522
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16639812
DOI:10.3389/fphar.2017.00807