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Regulatory Effect of Common Promoter Polymorphisms on the Expression of the 11 beta-Hydroxysteroid Dehydrogenase Type 1 Gene

Cited 16 time in Web of Science Cited 19 time in Scopus
Authors

Ku, Yun Hyi; Koo, Bo Kyung; Kwak, Soo Heon; Cho, Young Min; Lee, Hong Kyu; Choi, Jung-Won; Park, Kyong Soo; Oh, Bermseok; Kim, Yeonjung; Shin, Hyoung Doo

Issue Date
2009
Publisher
KARGER
Citation
HORMONE RESEARCH; Vol.72 1; 25-32
Keywords
11 beta-Hydroxysteroid dehydrogenase type 1ObesityDiabetes mellitus, type 2Polymorphism
Abstract
Background/Aims: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and type 2 diabetes and metabolic phenotypes in Koreans. Methods: We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.-19835G>A, g.-19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genotyped in 757 subjects with type 2 diabetes and 644 nondiabetic subjects. Results: There was no association between the 4 common polymorphisms of HSD11B1 and type 2 diabetes. g.-19835G>A and g.-19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haplotype construct carrying both g.-19835A and g.-19609G showed significantly decreased promoter activity compared to other common haplotype constructs. Conclusion: The variations in HSD11B1 were not associated with susceptibility to type 2 diabetes or metabolic phenotypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression. Copyright (C) 2009 S. Karger AG, Basel
ISSN
0301-0163
Language
English
URI
https://hdl.handle.net/10371/76336
DOI
https://doi.org/10.1159/000224337
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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