Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation.
A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3...
| Հիմնական հեղինակներ: | , , , , , , |
|---|---|
| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
2001
|
| _version_ | 1826300131352248320 |
|---|---|
| author | Hunter, D De Lange, M Snieder, H MacGregor, A Swaminathan, R Thakker, R Spector, T |
| author_facet | Hunter, D De Lange, M Snieder, H MacGregor, A Swaminathan, R Thakker, R Spector, T |
| author_sort | Hunter, D |
| collection | OXFORD |
| description | A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets. |
| first_indexed | 2024-03-07T05:12:30Z |
| format | Journal article |
| id | oxford-uuid:dc09d89e-932e-4c0e-a8aa-ee4f286d7119 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:12:30Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:dc09d89e-932e-4c0e-a8aa-ee4f286d71192022-03-27T09:14:56ZGenetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dc09d89e-932e-4c0e-a8aa-ee4f286d7119EnglishSymplectic Elements at Oxford2001Hunter, DDe Lange, MSnieder, HMacGregor, ASwaminathan, RThakker, RSpector, TA classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets. |
| spellingShingle | Hunter, D De Lange, M Snieder, H MacGregor, A Swaminathan, R Thakker, R Spector, T Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title | Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title_full | Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title_fullStr | Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title_full_unstemmed | Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title_short | Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. |
| title_sort | genetic contribution to bone metabolism calcium excretion and vitamin d and parathyroid hormone regulation |
| work_keys_str_mv | AT hunterd geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT delangem geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT sniederh geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT macgregora geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT swaminathanr geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT thakkerr geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation AT spectort geneticcontributiontobonemetabolismcalciumexcretionandvitamindandparathyroidhormoneregulation |