Difference in Height Associated with a Translation Start Site Polymorphism in the Vitamin D Receptor Gene1

Abstract

The function of 1,25-dihydroxyvitamin D3 in bone development is to regulate the differentiation or proliferation of osteoblastic, osteoclastic, and chondrocytic lineage, affecting bone mineralization and linear bone growth. An A(T/C)G substitution exists in the first of the two putative translation initiation sites in exon 2 of the vitamin D receptor (VDR) gene. We studied the relationship between exon 2 polymorphism and height in 90 healthy Japanese female subjects aged 18-20 y, who had attained final height, in 159 healthy Japanese aged 13 y, and 24 children with constitutional short stature aged 6-10 y less than -1.5 SD in height, mostly with parents of normal height. Exon 2 polymorphism was analyzed by PCR-single strand conformation polymorphism, PCR-direct sequencing, and PCR-restriction fragment length polymorphism. The frequency of the exon 2 polymorphism was genotype CC (ACG/ACG), 0.37; genotype CT (ACG/ATG), 0.51; and genotype TT (ATG/ATG), 0.12 in 249 normal subjects. The mean height of female subjects aged 18-20 y with the genotype CT was 160.3 +/- 4.3 cm (mean +/- SD), whereas that with CC was 4.4 cm lower (p < 0.0001), and that with TT was 2.7 cm lower (p = 0.0302). At age 13 y, this trend was observed, and the mean height SD score of subjects with the genotype CT was taller than homozygotes (CC/CT; p = 0.0363 and CT/TT; p = 0.0208) in 159 subjects. Genotype CT in 24 children with constitutional short stature was less frequent than other genotypes (CC, 0.62; CT, 0.21; TT. 0.17) (chi 2 p value, 0.0171). In conclusion, the exon 2 polymorphism affecting the VDR mRNA and protein is one of the major determinants of adult height at least in female Japanese, which was noted at the age of 13 y examined in both sexes.

Association between Circulating Vitamin D, the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

“…Taq1 gene polymorphism genotypes frequencies differ among different ethnicities, different cancer types (Bid et al, 2005), and methodology by which Taq1 VDR polymorphism was investigated, sample size and vitamin D serum levels (Onen et al, 2008). Among Indian individuals the frequencies of Taq1 variants were 49%, 43% and 8% (Bhanushali et al, 2010) while Japanese study showed 77%, 22% and 1% (Minamitani et al, 1998) and a Turkish, study showed frequency of 40.8%, 47.9% and 11.2% (Dilmec et al, 2009) for TT, Tt and tt respectively.…”

Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study

“…Environmental factors, such as improved nutrition, have led to a progressive increase in height, but the genetic contribution to height is still remarkable, and variations in a number of genes have been associated with height: DRD2, which encodes the dopamine D2 receptor [31]; VDR, which encodes the vitamin D receptor [32]; COL1A1, which encodes the α1-chain of type I collagen [33]; ESR1, which encodes the α-chain of the oestrogen receptor [34]; and LHB, which encodes the luteinizing hormone beta polypeptide [35].…”

Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation

“…DNA was prepared from archival frozen material using conventional techniques (SDS lysis, proteinase K digestion, phenol/chloroform extraction and ethanol precipitation). PCR for the relevant regions of the VDR gene and restriction enzyme digestion of the products were done essentially as described for the FokI, 1 BsmI, 2 ApaI 3 and TaqI. 3 RFLPs.…”

“…3,4,7 Reduced bone loss associated with liver transplantation is less frequent in transplant patients who possess the BsmI and ApaI aa and bb genotypes for VDR. 8 Polymorphism at the ATG initiation codon (FokI site) has been associated with genetic determination of final height in Japanese subjects, with heterozygotes at this locus achieving a greater final height than homozygotes for either allele, 1 and with heritable variation in bone mineral density. 9 Polymorphism at both the FokI and TaqI sites has been associated with variation in intervertebral disc degeneration in males.…”