Association of gene polymorphisms and bone density in Japanese girls

Katsumata, Kiyoe; Nishizawa, Keitaro; Unno, Atsushi; Fujita, Yūkō; Tokita, Akifumi

doi:10.1007/s007740200023

Cited by 46 publications

(38 citation statements)

References 18 publications

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“…Moreover, PTH BstB1 polymorphisms also showed a significant interaction on serum PTH (p = 0.010). These results support previous findings in Japanese girls [47].…”

Section: Bone Mineral Densitysupporting

confidence: 95%

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Noordin

Glowacki

2015

Rheumatol Int

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Parathyroid glands secrete parathyroid hormone (PTH) which plays multiple roles in calcium homeostasis and in bone remodeling. Secretion of PTH is regulated by extracellular calcium levels and other humoral factors including 1α,25(OH)2D3. PTH regulates gene expression and induces biological effects directly and indirectly. The human gene encoding PTH is located on chromosome 11. In this review, we study the diverse PTH along with its receptor gene polymorphisms and their association with osteoporosis and fracture healing. Genetic factors are associated with osteoporosis by influencing bone mineral density (BMD), bone turnover, calcium homeostasis, and susceptibility to osteoporotic fractures. Polymorphisms in genes encoding PTH may contribute to genetic regulation of BMD and thus susceptibility to fracture risk. PTH stimulates the proliferation of osteoprogenitor cells, production of alkaline phosphatise, and bone matrix proteins that contribute to hard callus formation and increases strength at the site of fractured bone. During remodeling, PTH promotes osteoclastogenesis restoring the original shape, structure, and mechanical strength of the bone. Some PTH polymorphisms have shown an association with fracture risk. Further research is needed to elucidate the relative importance of PTH genetics and the mechanisms of genetic contributions to gene-gene interactions in the pathogenesis of osteoporosis and in fracture healing.

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“…Moreover, PTH BstB1 polymorphisms also showed a significant interaction on serum PTH (p = 0.010). These results support previous findings in Japanese girls [47].…”

Section: Bone Mineral Densitysupporting

confidence: 95%

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Noordin

Glowacki

2015

Rheumatol Int

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“…This result supports previous findings in American premenopausal women [26] , Japanese postmenopausal women [27] and in Japanese girls [29] . However, we were not able to replicate the association between BstBI polymorphism and BMD in females, but were the first to show this association also in males.…”

Section: Discussionsupporting

confidence: 83%

“…Moreover, PTH activates osteoblasts and stimulates osteoclast formation and resorption [25] . Only a few studies have shown an association between PTH BstBI polymorphism and BMD or bone dimensions [26][27][28][29] , while other studies have shown no such associations [30] .Thus far, numerous association studies examining the genetic susceptibility to osteoporosis on the population level have yielded inconclusive results [31] . This could partly be attributed to the heterogeneity of the genetic background of the population, for example, due to genetic stratification in recently admixed populations [32] .…”

mentioning

confidence: 96%

Associations of Vitamin D Receptor, Calcium-Sensing Receptor and Parathyroid Hormone Gene Polymorphisms with Calcium Homeostasis and Peripheral Bone Density in Adult Finns

Laaksonen

Outila²,

Kärkkäinen³

et al. 2009

Lifestyle Genomics

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Background: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. Methods: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31–43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. Results: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene–gene or diet–gene interactions studied showed no significant results. Conclusions: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.

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“…Several polymorphisms have been described in the gene encoding PTH, which may influence not only the secretion rate of the hormone in response to the CaSR signaling but also the efficiency of the hormone, as has been shown in bone metabolism studies (Katsumata et al 2002) and familial isolated hypoparathyroidism (FIH) (Miric & Levine 1992). This syndrome, characterized by hypocalcemia and hyperphosphatemia due to an inherited deficient secretion of biologically active parathormone, has been related to PTH gene mutations and polymorphisms (Ahn et al 1986, Sunthornthepvarakul et al 1999.…”

Section: Introductionmentioning

confidence: 99%

A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms

Alvarez-Hernandez¹,

Santamaría²,

Rodríguez‐García³

et al. 2003

Journal of Molecular Endocrinology

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A novel missense activating mutation in the extracellular calcium-sensing receptor (CaSR) is reported in this work. It was identified in three related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). The proband, a 27-year-old woman, diagnosed as having hypoparathyroidism at 7 years of age and a history of seizures, showed the highest penetrance of the mutation. The remaining two affected members presented asymptomatic chronic hypocalcemia despite severe hypoparathyroidism associated with high levels of serum phosphate and calcium urinary excretion. The missense mutation (Glu 604 Lys) affected an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular amino-terminal domain, which seems to be required for the coupling of ligand binding to the activation of intracellular signaling pathways. This genetic change cosegregated with hypocalcemia in all the individuals where the mutation was found. As parathyroid hormone (PTH) secretion is the regulatory target of the CaSR, polymorphism analysis of the PTH gene was carried out. PTH polymorphisms were analyzed in the kindred studied. Affected members for the Glu 604 Lys CaSR mutation which also carried the uncommon PTH alleles showed higher penetrance of the mutation, with more severe autosomal dominant hypocalcemia. These results suggested that the PTH gene could act as a modifier locus of ADH, affecting the penetrance of the activating CaSR mutation described.

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Association of gene polymorphisms and bone density in Japanese girls

Cited by 46 publications

References 18 publications

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Associations of Vitamin D Receptor, Calcium-Sensing Receptor and Parathyroid Hormone Gene Polymorphisms with Calcium Homeostasis and Peripheral Bone Density in Adult Finns

A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms

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