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A large‐scale population‐based study of the association of vitamin D receptor gene polymorphisms with bone mineral density
Author(s) -
Uitterlinden André G.,
Pols Huibert A. P.,
Burger Huibert,
Huang Qiuju,
van Daele Paul L. A.,
van Duijn Cornelia M.,
Hofman Albert,
Birkenhäger Jan C.,
van Leeuwen Johannes P. T. M.
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110908
Subject(s) - calcitriol receptor , taqi , allele , haplotype , genetics , locus (genetics) , restriction fragment length polymorphism , genotype , biology , bone mineral , population , allele frequency , medicine , osteoporosis , endocrinology , gene , environmental health
Abstract Conflicting results have been reported on the association between restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus (i.e., for Bsm I, Apa I, and Taq I) and bone mineral density (BMD). We analyzed this association in a large population‐based sample ( n = 1782) of men and women aged 55–80 years using a novel direct haplotyping polymerase chain reaction (PCR) test to monitor the three polymorphic sites simultaneously. The direct haplotyping test we developed demonstrated a larger degree of genetic polymorphism at the VDR gene locus than described until now. None of the individual RFLPs were associated with BMD at the proximal femur. By analyzing allele dose effects, we identified a VDR haplotype allele weakly associated with low BMD. This allele, as one representative of the group of b alleles, is different from the Bsm I allele previously reported by other groups to be associated with low BMD. This suggests allelic heterogeneity at the VDR locus in relation to BMD. Our results indicate at most a small effect of the VDR genotype on BMD in this elderly population. Since anonymous polymorphisms were analyzed, alternative explanations for our results include linkage to another nearby bone‐metabolism related gene.