Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density

M Piedra; M T Garcia-Unzueta; A Berja; J A Riancho; C Valero; B Paule; B A Lavin; J A Amado

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Endocrine Abstracts (2011) 26 P500

ECE2011 Poster Presentations Bone/calcium/Vitamin D (58 abstracts)

Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density

M Piedra ¹ , M T García-Unzueta ³ , A Berja ¹ , J A Riancho ^2, , C Valero ² , B Paule ¹ , B A Lavín ³ & J A Amado ^1,

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Author affiliations

¹Endocrinology Service ‘Marqués de Valdecilla’ University Hospital, Santander, Spain; ²Internal Medicine Service ‘Marqués de Valdecilla’ University Hospital, Santander, Spain; ³Clinical Biochemistry Service ‘Marqués de Valdecilla’ University Hospital, Santander, Spain; ⁴University of Cantabria, Santander, Spain.

Background: Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that 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 and RANKL 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 163 A/G, 245 T/G and 1181 G/C SNPs of the OPG gene and the rs2277438 SNP of the RANKL gene, 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: 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 heterozygotes in both OPG 163 A/G and OPG 245 T/G SNPs in those with PHPT but not in control subjects. We found no difference between genotypes of the OPG 1181 G/C SNP with regard to BMD in the PHPT subjects. However, we did find higher BMD in the lumbar spine in the CC than in the GG genotype group in the control subjects.

Conclusions: Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and GG genotype for the OPG 163 A/G and 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.