دورية أكاديمية
أعرض في EDS

Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels.

التفاصيل البيبلوغرافية
العنوان: Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels.
المؤلفون: Böhm A; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany., Ordelheide AM, Machann J, Heni M, Ketterer C, Machicao F, Schick F, Stefan N, Fritsche A, Häring HU, Staiger H
المصدر: PloS one [PLoS One] 2012; Vol. 7 (3), pp. e34035. Date of Electronic Publication: 2012 Mar 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Genetic Variation*, Adiposity/*genetics , Eye Proteins/*genetics , Insulin Resistance/*genetics , Leptin/*blood , Nerve Growth Factors/*genetics , Obesity/*physiopathology , Serpins/*genetics, Adult ; Female ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
مستخلص: Objective: Pigment epithelium-derived factor (PEDF) belongs to the serpin family of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance. Therefore, we assessed whether common genetic variation within the SERPINF1 locus contributes to adipose tissue-related prediabetic phenotypes in humans.
Subjects/methods: A population of 1,974 White European individuals at increased risk for type 2 diabetes was characterized by an oral glucose tolerance test with glucose and insulin measurements (1,409 leptin measurements) and genotyped for five tagging SNPs covering 100% of common genetic variation (minor allele frequency ≥ 0.05) in the SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance imaging (MRI) and spectroscopy (MRS).
Results: After adjustment for gender and age and Bonferroni correction for the number of SNPs tested, SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass (p = 0.0094) and fasting leptin concentrations (p = 0.0035) as well as nominal associations with bioelectrical impedance-derived percentage of body fat (p = 0.0182) and clamp-derived insulin sensitivity (p = 0.0251). The association with insulin sensitivity was completely abolished by additional adjustment for body fat (p = 0.8). Moreover, the fat mass-increasing allele of SNP rs12603825 was significantly associated with elevated fasting PEDF concentrations (p = 0.0436), and the PEDF levels were robustly and positively associated with all body fat parameters measured and with fasting leptin concentrations (p<0.0001, all).
Conclusion: In humans at increased risk for type 2 diabetes, a functional common genetic variant in the gene locus encoding PEDF contributes to overall body adiposity, obesity-related insulin resistance, and circulating leptin levels.
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المشرفين على المادة: 0 (Eye Proteins)
0 (Leptin)
0 (Nerve Growth Factors)
0 (Serpins)
0 (pigment epithelium-derived factor)
تواريخ الأحداث: Date Created: 20120330 Date Completed: 20120803 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3311576
DOI: 10.1371/journal.pone.0034035
PMID: 22457810
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0034035