title: HSD11B1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without a clinically apparent hypercortisolemia.
abstract: BACKGROUND
  Endogenous glucocorticoid (GC) may participate in bone physiology, even in subjects with no glucocorticoid excess. 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) is a primary regulator catalyzing the reduction of inactive cortisone to active cortisol. To elucidate genetic relevance of HSD11B1 variants to vertebral fracture and osteoporosis, we investigated the potential involvement of six HSD11B1 SNPs in postmenopausal women.
  
  
  METHODS
  All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Six polymorphisms were selected and genotyped in all study participants (n=1329). BMD was measured using dual-energy X-ray absorptiometry.
  
  
  RESULTS
  HSD11B1 +16374C>T and +27447G>C were associated with reduced vertebral fracture risk (p=0.016 and 0.032, respectively). Two of these (LD block2) in intron 5 (rs1000283 and rs932335) were significantly associated with bone mineral density (BMD) at the femoral neck (p=0.00005 and 0.0002, respectively). Specifically, HSD11B1 +16374C>T and +27447G>C polymorphisms were associated with higher BMD values of the femoral neck in multiple comparison (p=0.0002 and 0.0004, respectively) and Bonferroni corrected significance level (97% power). Consistent with these results, HSD11B1-ht21 and -ht22 comprising both SNPs also showed the evidence of association with BMD values of the femoral neck (p(domiant)=0.0002 and p(recessive)=0.00005, respectively).
  
  
  CONCLUSIONS
  Our results provide preliminary evidence supporting an association of HSD11B1 with osteoporosis in postmenopausal women. Also, these findings demonstrate that +16374C>T polymorphism may be useful genetic markers for bone metabolism.
authors: The Center for Genome Science, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea.
authors: Joo-Yeon
authors: JY
authors: Hwang
authors: Seung Hun
authors: SH
authors: Lee
authors: Ghi Su
authors: GS
authors: Kim
authors: Jung-Min
authors: JM
authors: Koh
authors: Min Jin
authors: MJ
authors: Go
authors: Young-Jin
authors: YJ
authors: Kim
authors: Hyung-Cheol
authors: HC
authors: Kim
authors: Tae-Ho
authors: TH
authors: Kim
authors: Jung Min
authors: JM
authors: Hong
authors: Eui Kyun
authors: EK
authors: Park
authors: Jong-Young
authors: JY
authors: Lee
authors: Shin-Yoon
authors: SY
authors: Kim
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D003480:Cushing Syndrome / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D050723:Fractures, Bone / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D016103:Spinal Fractures / Q000201:enzymology / Q000235:genetics
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1