The <i>Alu</i>I Calcitonin Receptor Gene Polymorphism (TT) Is Associated with Low Bone Mineral Density and Susceptibility to Osteoporosis in Postmenopausal Women

Abstract

Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of theAluI calcitonin receptor gene polymorphism to bone mineral density and their relationship to osteoporosis. We determined the AluI calcitonin receptor gene polymorphism using polymerase chain reaction-based restriction analysis in 167 postmenopausal women in Taiwan. The polymorphism was detected by the restriction enzyme AluI, where the C allele indicated the absence of the cuttable site and the T allele indicated its presence. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. The allelic frequencies for the 167 postmenopausal women in Taiwan were 86.5% for C and 13.5% for T in AluI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was 2.4% TT, 22.2% CT, and 75.4% CC. The three genotypic groups differed significantly in unadjusted and adjusted bone mineral density at the lumbar spine and the femoral neck. Unadjusted and adjusted bone mineral density values were lowest in women with the TT genotype. The AluI calcitonin receptor genotype showed a positive association with prevalence of osteoporosis in the subjects. That is, women with genotype TT had a greater risk for developing osteoporosis at the lumbar spine and at the femoral neck. The AluI calcitonin receptor gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis, but should be interpreted with caution because of the small number of subjects in the unfavorable TT genotype.

Genetic background influences metabolic response to dietary phosphorus restriction

“…The three most significant changes in gene expression that were based on dietary P deficiency and its interaction with genetic background were seen in CALCR, VDR and IGFBP3. Polymorphisms in the human CALCR gene and VDR gene have been shown to be associated with BMD [53][54][55][56][57][58]. Based on the expression data, CALCR, VDR and IGFBP3 are good candidates for single nucleotide polymorphism studies.…”

Genetic predisposition for femoral neck stress fractures in military conscripts

“…Several studies report an association between the CTR polymorphism Alu I and lumbar spine and femoral neck BMD in both men and women, but the reports have been somewhat contradictory. Studies in postmenopausal women revealed that the CC genotype is more common in non-osteoporotic women than the TT genotype [30,31], and that the TT genotype is associated with lower lumbar spine and femoral neck BMD and increases the predisposition for osteoporosis [32,33]. The opposite finding was suggested by Braga et al [34] who reported that the CC genotype is associated with decreased BMD and is more common in men with hip or vertebral fractures than in control subjects [34].…”

Association between an <i>Alu</i>I Polymorphism in the Calcitonin Receptor Gene and Quantitative Ultrasound Parameters in Korean Men

“…Thus, the present data supported the protective effect of this allele on the risk factor of osteoporosis according to nutritional condition. There are many reports on the association between this polymorphism and BMD or osteoporosis in mainly postmenopausal women with inconsistent results [3,7,[17][18][19][20][21][22][23] . Because this polymorphism is located within the fourth intracellular domain of CTR [6] , and plays an important role in the binding of CT, the significant association between this polymorphism and some bone phenotypes in our study may reflect the functional role such as ligand binding activity.…”

“…Genotype Analysis of CTR AluI RFLP Genomic DNA was prepared from buffy coats from blood (5 ml) and then was screened for the CTR Alu I polymorphism using PCR reaction, followed by Alu I digestion, according to a previously published protocol [7] .…”

“…Nakamura et al [6] reported an Alu I polymorphism characterized by a single nucleotide transition (C to T polymorphism) at position 1377 of human CTR cDNA in the Japanese population. Subsequently, this polymorphism has been used as genetic marker for several clinical association studies such as osteoporosis [7] and breast cancer [8] .…”