title: Regulatory effect of common promoter polymorphisms on the expression of the 11beta-hydroxysteroid dehydrogenase type 1 gene.
abstract: OBJECTIVE
  Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11beta-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.
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Yun Hyi
authors: YH
authors: Ku
authors: Bo Kyung
authors: BK
authors: Koo
authors: Soo Heon
authors: SH
authors: Kwak
authors: Young Min
authors: YM
authors: Cho
authors: Hyoung Doo
authors: HD
authors: Shin
authors: Hong Kyu
authors: HK
authors: Lee
authors: Yeonjung
authors: Y
authors: Kim
authors: Jung-Won
authors: JW
authors: Choi
authors: Bermseok
authors: B
authors: Oh
authors: Kyong Soo
authors: KS
authors: Park
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human