title: TNFRSF11B gene polymorphisms 1181G > C and 245T > G as well as haplotype CT influence bone mineral density in postmenopausal women.
abstract: OBJECTIVE
  Osteoprotegerin (OPG) inhibits osteoclast function by acting as a decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL), thus being an important candidate gene for osteoporosis. Three recent genome-wide association studies also identified the TNFRSF11B gene, coding for OPG, as playing a key role in bone mineral density (BMD) regulation. As variations in the TNFRSF11B gene could alter the susceptibility to osteoporosis, the aim of study was to investigate association of two TNFRSF11B gene polymorphisms with BMD and serum OPG concentration in postmenopausal women.
  
  
  METHODS
  478 postmenopausal women were genotyped for the presence of TNFRSF11B gene polymorphisms 245T > G (rs3134069) and 1181G > C (rs2073618). BMDs and serum OPG concentrations were measured.
  
  
  RESULTS
  Two common haplotypes GT and CT occurred in 41.2% and 52.4% of subjects. In osteoporotic postmenopausal women, lumbar spine BMD was associated with polymorphisms 245T > G and 1181G > C, as well as with CT haplotype (p values 0.013, 0.006 and 0.006, respectively). Additionally, femoral neck BMD showed the association with 245T > G (p = 0.047). No other statistically significant associations with BMD were found for the studied SNPs and haplotypes. No association with serum OPG concentration was shown in any of the studied groups.
  
  
  CONCLUSIONS
  Our results suggest that, in postmenopausal osteoporosis, polymorphisms 245T > G and 1181G > C, as well as haplotype CT in TNFRSF11B gene influence BMD.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Department of Clinical Biochemistry, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia. simona.mencej@ffa.uni-lj.si
authors.forename: Simona
authors.initials: S
authors.lastname: Mencej-Bedrač
authors.forename: Janez
authors.initials: J
authors.lastname: Preželj
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005272:Femur Neck; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008159:Lumbar Vertebrae; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000235:genetics*; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human