Osteoprotegerin ‘relevant’ in osteoporosis phenotypes
MedWire News: Spanish researchers have identified polymorphisms and haplotypes in the osteoprotegerin gene (OPG) that are associated with bone mineral density (BMD) and osteoporotic fractures.
Osteoprotegerin plays a key role in bone remodeling, but analyses of the association between OPG single nucleotide polymorphisms (SNPs) and BMD, fracture, or other phenotypes have produced varying results, note Susana Jurado (Institut Municipal d’Investigació Mèdica, Barcelona) and colleagues.
In the present study, Jurado and team genotyped 964 postmenopausal Spanish women for 24 SNPs and six haplotypic blocks in OPG and tested their association with lumbar spine BMD, femoral neck BMD, and osteoporotic fragility fractures.
The researchers report that, after adjustment for multiple testing, the C allele of SNP rs1032129 was significantly associated with reduced femoral neck BMD.
Two haplotypes were significantly associated with femoral neck BMD and two with fracture. The most significant was the AC haplotype in block 4 (containing SNPs rs1032129 and rs1032128), which was strongly associated with reduced femoral neck BMD compared with individuals homozygous for the major haplotype GA.
“This result matches that of SNP rs1032129 but with improved significance and suggests that the risk factor may be the haplotype and not the SNP alone,” comment Jurado and co-investigators in the journal Osteoporosis International.
In block 5, two distinct haplotypes, AACG and TACG, appeared as risk factors for low femoral neck BMD and for fracture, respectively, when compared with the homozygotes of the major haplotype AGCA.
Finally, in block 2, haplotype GAAGAGTG was associated with significantly increased risk for fracture when compared to the major haplotype AGGGAAGC.
A global assessment of the results indicated that all the alleles and haplotypes with a protective effect belonged to a frequent long-range haplotype.
Jurado et al conclude: “These findings confirm the relevance of osteoprotegerin in osteoporosis phenotypes.”
They add: “The challenge remains to determine whether any of the SNPs addressed here, other undetected SNP(s) captured by the haplotypes or a combination of SNPs can explain these findings.”
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By Laura Dean