Publication
Title
Identification and functional characterization of a missense mutation in resistin in two patients with severe obesity and insulin resistance
Author
Abstract
Objective In this study, we hypothesized that mutations in the resistin encoding gene, RETN, may cause a monogenic form of obesity. Design/methods We screened the coding region of RETN in 81 morbidly obese adults, 263 overweight and obese children/adolescents, and 116 healthy lean subjects. In vitro experiments include qPCR, ELISA, and western blot for WT and mutant resistin transfected into 3T3-L1 adipocytes. Results Mutation analysis identified five sequence variants in our patient populations: 3′-UTR +87 G/A, 3′-UTR +100 A/G, T73T, IV3-61 C/A, and C78S. In our control population, we only found the 3′-UTR +87 G/A variant. We started functional experiments for the C78S mutation that was found in a 20-year-old obese male (body mass index (BMI)=39.7 kg/m2) and his obese mother (BMI=31.9 kg/m2). In vitro testing demonstrated that the mutation does not impair mRNA expression. We identified a 100-fold lower extracellular protein concentration for mutant resistin compared with WT levels using a resistin ELISA on cell culture medium (P=4.87×10−6). We also detected a decreased intracellular concentration for the mutant protein (tenfold lower relative levels, P=0.007). The plasma resistin levels of the proband and his mother, however, did not differ significantly from lean control individuals. Conclusions In conclusion, we identified the first missense mutation in resistin in a morbidly obese proband and his obese mother. Functional testing of the mutant protein suggests that the C78S mutant protein is degraded, possibly resulting in a decreased extracellular concentration, which may predispose to obesity.
Language
English
Source (journal)
European journal of endocrinology. - Copenhagen
Publication
Copenhagen : 2011
ISSN
0804-4643
Volume/pages
164:6(2011), p. 927-936
ISI
000291020500010
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 14.07.2011
Last edited 21.09.2017
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