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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-08-0021v1 159/2/187    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lazáry, A. Articles by Lakatos, P. PubMed PubMed Citation Articles by Lazáry, A. Articles by Lakatos, P.

Single nucleotide polymorphisms in new candidate genes are associated with bone mineral density and fracture risk

Áron Lazáry^1,2,*, János P Kósa^1,*, Bálint Tóbiás¹, Judit Lazáry³, Bernadett Balla¹, Krisztián Bácsi¹, István Takács¹, Zsolt Nagy¹, Tibor Mez¹, Gábor Speer¹ and Péter Lakatos¹

¹ 1st Department of Internal Medicine, Semmelweis University, Koranyi S. u. 2/a., Budapest H-1083, Hungary² National Center for Spinal Disorders, Buda Health Center, Budapest H-1126, Hungary³ Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest H-1089, Hungary

(Correspondence should be addressed to Á Lazáry; Email: lazaron{at}bel1.sote.hu)

Objective: Osteoporosis (OP) is a multifactorial disease with high heritability but its exact genetic background is still poorly understood. We examined the effect of 24 single nucleotide polymorphisms (SNPs) located in five genes – alkaline phosphatase, matrix metalloproteinase-2, tissue inhibitor of metalloproteases-2 (TIMP2), fibroblast growth factor receptor-1 (FGFR1), and fatty acid-binding protein-3 (FABP3) – previously not associated with OP.

Design: We performed a genotype–phenotype association study at a university hospital.

Methods: A total of 360 Hungarian postmenopausal women were involved in the study. Bone mineral density (BMD) was determined at spine, hip, and distal radius. Genomic DNA was extracted from venous blood samples and a high-throughput genotyping method based on single-based primer extension was applied for allelic discrimination. Robust statistical tools were utilized for multiplex data analysis.

Results: SNP rs6996321 in FGFR1 was significantly related to spine BMD (P=0.002) and rs10914367 in FABP3 was associated with hip BMD (P=0.028). Non-vertebral fracture risk was significantly increased in carriers of ‘A’ allele of rs9900972 in TIMP2 (odds ratio=2.06, P=0.0187). We could also identify validated gene–gene interactions significantly affecting BMD and fracture risk.

Conclusions: We identified two previously unreported SNPs in FGFR1 and FABP3 associated with BMD and a third SNP in TIMP2 related to risk for non-vertebral osteoporotic fractures. This is the first report about the association between these allelic variants and the phenotypes of postmenopausal OP. Further studies need to clarify the role of these genes and their polymorphisms in the process of bone loss.