title: "Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density".
abstract: BACKGROUND
  Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT.
  
  
  METHODS
  We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.
  
  
  RESULTS
  Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).
  
  
  CONCLUSIONS
  Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.
authors.affiliation: Endocrinology Service, University Hospital Marqués de Valdecilla University of Cantabria-IFIMAV, Avda, de Valdecilla, Santander 39008, SPAIN.
authors.forename: María
authors.initials: M
authors.lastname: Piedra
authors.forename: María T
authors.initials: MT
authors.lastname: García-Unzueta
authors.forename: Ana
authors.initials: A
authors.lastname: Berja
authors.forename: Blanca
authors.initials: B
authors.lastname: Paule
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Lavín
authors.forename: Carmen
authors.initials: C
authors.lastname: Valero
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
authors.forename: José A
authors.initials: JA
authors.lastname: Amado
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D050723:Fractures, Bone; D005838:Genotype; D006720:Homozygote; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics*; D020347:Lithiasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D053244:Osteoprotegerin / Q000235:genetics*; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D053245:RANK Ligand / Q000235:genetics*
chemical_list: D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand