Vitamin D receptor start codon polymorphism ( Fok I) is related to bone mineral density in healthy adolescent boys

Abstract

Peak bone mass is considered a major determinant in the emergence of osteoporosis and is mainly genetically regulated. Several genes have been investigated, among them the vitamin D receptor ( VDR) gene. A single-nucleotide polymorphism (defined by the endonuclease FokI) located in the start codon of the VDR creates the alleles F and f, resulting in different proteins. A number of previous studies have proved the F allele to be more advantageous as concerns bone mineral density (BMD). In this longitudinal study of 88 adolescent boys, we have investigated whether the different genotypes are associated with BMD, bone mineral content (BMC), or bone area. BMD, BMC, and bone area of the right femoral neck, lumbar spine, and total body were measured using dual-energy X-ray absorptiometry. Differences in phenotypes in relation to the FokI polymorphism were calculated by means of an analysis of variance (ANOVA), with Bonferroni's correction for multiple comparisons. At the first examination, the FokI genotypes were significantly related to lumbar spine BMC and total body bone area in boys aged 16.9 +/- 0.3 years (mean +/- SD). There was a strong tendency towards significance as regards pubertal stage, total body and femoral neck BMC, weight, lean body mass, lumbar spine bone area, and lumbar spine BMD. There were no significant differences in height, fat mass, birth height and weight, total body and femoral neck BMD, and femoral neck bone area. Regression analysis proved the FokI genotypes to be independently related to lumbar spine BMD ( FF > ff; P < 0.01), and possibly total body BMD ( P = 0.06), but not femoral neck BMD. At the second examination, approximately 2 years later, our ANOVA results showed significance as regards femoral neck BMC and weight. Using multiple regression, the FokI genotypes were independently related to lumbar spine BMD ( FF > ff; P = 0.03), and total body BMD ( P < 0.05), but not femoral neck BMD. This study proves the FokI polymorphism to be an independent predictor of lumbar spine BMD are probably total body BMD, but not femoral neck BMD.

Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis

“…However, no significant differences were observed between patients and controls in terms of the genotype frequencies of the FokI and Cdx2 polymorphisms, and the genotypes of these two polymorphisms were not found to influence LSBMD or FNBMD in patients. Our findings concur with those of some previous studies, but not all of these studies assessed relationships in adolescent girls [2,22,25,28,34].…”

“…However, the majority of these studies involved adults rather than children [2,22,25,34]. Nevertheless, published results are conflicting, regardless of age, and in children appear to differ by gender, pubertal status and the restriction enzyme used [2,22,25,34]. Thus, in the present study, we enrolled an age-and sex-matched healthy control group to minimize these effects.…”

“…Laaksonen et al [22] concluded that the VDR FokI polymorphism is not associated with BMD or quantitative ultrasound parameters in girls, whereas Ames et al [2] found that the FokI polymorphism at the VDR translation initiation site was associated with BMD and calcium deposition in children. On the other hand, Strandberg et al [34] concluded that FokI genotypes are independently related to LSBMD, but not to FNBMD.…”

“…The VDR gene is one of the most widely studied osteoporosis-related genes. However, the numerous genetic association studies undertaken on the topic have yielded conflicting results [2,22,25,34,37,44]. Arabi et al [3] concluded that VDR gene polymorphisms, identified using BsmI restriction enzyme, are associated with the bone mineral contents of the lumbar spine and femoral neck in healthy girls, whereas Lorentzon et al [25] reported that the VDR gene polymorphism defined by ApaI and BsmI, is related to LSBMD in healthy adolescent girls.…”

“…Several investigators have evaluated the association between VDR gene polymorphisms and BMD in postmenopausal women, and a smaller number of studies have been conducted in children [2,22,25,34,37,44]. However, no report has yet linked bone mass in AIS and a VDR gene polymorphism.…”