Single nucleotide polymorphisms of the OPG-RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral densityReportar como inadecuado




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BMC Medical Genetics

, 12:168

Genetic epidemiology and genetic associations

Abstract

BackgroundPrimary 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.

MethodsWe 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.

ResultsRegarding 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.

ConclusionsOur 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.

List of the abbreviationsP1NPAmino-terminal propeptyde type 1 Colagen

BMIBody mass index BAP: Bone alkaline phosphatase

BMDBone mineral density

IRMAImmunoradiometric assay

RANKLLigand of the receptor activator of nuclear factor-κβ OP: Osteoporosis

OPGOsteoprotegerin

PTHParathyroid hormone

PCRPolymerase chain reaction

PHPTPrimary hyperparathyroidism

RANKReceptor activator of nuclear factor-κβ

SNPSingle nucleotide polymorphism

ELISASpecific immunoassay

SDStandard deviation of the mean

SPSSStatistical Package for Social Sciences

DXAX-ray absorptiometry.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-12-168 contains supplementary material, which is available to authorized users.

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Autor: María Piedra - María T García-Unzueta - Ana Berja - Blanca Paule - Bernardo A Lavín - Carmen Valero - José A Rianch

Fuente: https://link.springer.com/







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