Vitamin D receptor alleles predict growth and bone density in girls   Commentary

Abstract

Twin and family studies suggest that up to 75% of the variance in bone mineral density (BMD) is determined genetically and several candidate genes have been identified that might be involved in this process.1 Polymorphisms of the vitamin D receptor (VDR) gene causing diVerences in bone density between the homozygous haplotypes, were first described by Morrison et al in twin studies in an older female population.2 Subsequently, over 50 studies have been reported, examining the relation between BMD and VDR genotypes at the polymorphism (Apa I, Bsm I, and Taq I) sites at intron 8/exon 9 and the Fok I site at exon 2. 3 Variable eVects have been reported: from no diVerence in BMD being attributable to the VDR alleles to a diVerence of ∼ 10% between the homozygous alleles. A meta-analysis of 16 published papers by Cooper and Umbach confirmed a small eVect of VDR alleles of ∼ 2-3% at the hip and lumbar spine, and less at the wrist. 4 Cooper and other researchers suggested that the eVect of the VDR allele might be more apparent in younger populations.

Insulin-Like Growth Factor Pathway Polymorphisms Associated with Body Size in Hispanic and Non-Hispanic White Women

“…In contrast to the findings of previous studies reporting that VDR genotype was related to height among children and adolescents (46,47), we found no association between VDR genotype and height. In our study, there was a lower mean BMI associated with the VDR BsmI B allele and an increased mean WHR among women with the VDR FokI ff genotype but only for Hispanics.…”

“…A polymorphism detected by the FokI restriction enzyme alters a translation initiation site (45). The VDR polymorphisms have been reported to influence growth and height in European and Australian Caucasian children (46,47). Several studies have reported that the untranslated region and/or the FokI polymorphisms are associated with cancer risk (48)(49)(50)(51)(52)(53)(54).…”

Selected risk factors of fractures in children — own observation

“…The impact of genetic determinants of bone tissue was evaluated in children and adolescents, because the optimal genetic effect is evident in children aged up to 20 years [21,22]. In studies conducted by Baroncelli et al, evaluating the association of VDR variability with bone mass in children in pre-pubertal period, no interactions have been reported between BsmI polymorphism and bone turnover markers (including osteocalcin), or bone mineral density [20].…”

Osteoporosis, genetics and hormones

“…Accordingly, a model taking into account the early influence of VDR-3 polymorphisms, calcium intake and puberty on BMD gain has been proposed to explain the relation between these genotypes and peak bone mass (Ferrari et al 1998a). Interestingly also, several investigators have noted a significantly lower height among women and men with the VDR-3 BB compared with Bb or bb genotypes (Barger-Lux et al 1995, Ferrari et al 1998c, Tao et al 1998, Lorentzon et al 2000. Considering the relationship between body size and bone size, as well as the influence of calcium intake on both body height and bone area during growth (Bonjour et al 1997), it is tempting to speculate that VDR-3 alleles together with environmental calcium might have an indirect and complex influence on peak bone mass through the regulation of skeletal growth.…”