Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin
Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-08, Vol.89 (15), p.6665-6669 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6669 |
|---|---|
| container_issue | 15 |
| container_start_page | 6665 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 89 |
| creator | Morrison, Nigel A. Yeoman, Rosanne Kelly, Paul J. Eisman, John A. |
| description | Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P $ |
| doi_str_mv | 10.1073/pnas.89.15.6665 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_16301348</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>2359849</jstor_id><sourcerecordid>2359849</sourcerecordid><originalsourceid>FETCH-LOGICAL-j261t-844de2703eaa1d8f36f4219594327274899786523032696721441f8eeea219533</originalsourceid><addsrcrecordid>eNpdkElPHDEQhS2USExIzlw4WCjKrYfy0l64jYawSAgQIlxbpscNHrntju0-zN_IL45ZlENOpVJ99areQ-iQwJKAZCdTMHmp9JK0SyFEu4cWBDRpBNfwCS0AqGwUp3wffcl5CwC6VbBAf9YxlOSe5uJiwHHAD8mE3Kz64sIzPjd9iQmvvLfeZlwivolpNB7fveyyiz4-u752jyY58-S8K7tT_OiKGV3AZ_je9nZ63b-wweK76HdjTNOLy2PGJmzw2qV-9ubt0m0uNlat3oWv6PNgfLbfPuoB-nX-82F92VzfXlytV9fNlgpSqhm-sVQCs8aQjRqYGDglutWcUUklV1pLJVrKgFGhhaSEczIoa615xRg7QD_edacUf882l250ubfem2DjnDsiGBDGVQWP_wO3cU6h_tbRSkgJwCv0_QMyufoYaoy9y92U3GjSrmu5FABtxY7esW2uyfwbU9ZqxTX7Cy3vi00</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201377004</pqid></control><display><type>article</type><title>Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin</title><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Morrison, Nigel A. ; Yeoman, Rosanne ; Kelly, Paul J. ; Eisman, John A.</creator><creatorcontrib>Morrison, Nigel A. ; Yeoman, Rosanne ; Kelly, Paul J. ; Eisman, John A.</creatorcontrib><description>Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P $<$ 0.0001) independent of age or menopause effects. Since the osteocalcin gene and the vitamin D receptor gene are encoded on different chromosomes, the interaction between these two genes occurs in trans. Thus, common alleles of this trans-acting factor, the vitamin D receptor, are functionally different and contribute to "normal" physiological variability in osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs indicates that the greater diversity in lumbar spine density between the dizygotic pairs can be explained by divergence in vitamin D receptor alleles. Variations in this receptor and other transacting factor genes may confound physiological studies of regulation of target genes and will need to be considered in future human and animal studies. This approach to genetic analysis provides a paradigm for the study of functional variation in trans-acting factors and the role such variation may play in the generation and evolution of physiological diversity.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.15.6665</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>1,25-dihydroxycholecalciferol ; Alleles ; Biological and medical sciences ; Bone density ; Bones ; Classical genetics, quantitative genetics, hybrids ; Fraternal twins ; Fundamental and applied biological sciences. Psychology ; Genes ; Genetic variation ; Genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Genotypes ; Human ; levels ; man ; Medical genetics ; Medical research ; osteocalcin ; Proteins ; Receptors ; restriction fragment length polymorphism ; trans-acting factor ; Vitamin D</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (15), p.6665-6669</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Aug 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359849$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359849$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5476005$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Morrison, Nigel A.</creatorcontrib><creatorcontrib>Yeoman, Rosanne</creatorcontrib><creatorcontrib>Kelly, Paul J.</creatorcontrib><creatorcontrib>Eisman, John A.</creatorcontrib><title>Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin</title><title>Proceedings of the National Academy of Sciences - PNAS</title><description>Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P $<$ 0.0001) independent of age or menopause effects. Since the osteocalcin gene and the vitamin D receptor gene are encoded on different chromosomes, the interaction between these two genes occurs in trans. Thus, common alleles of this trans-acting factor, the vitamin D receptor, are functionally different and contribute to "normal" physiological variability in osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs indicates that the greater diversity in lumbar spine density between the dizygotic pairs can be explained by divergence in vitamin D receptor alleles. Variations in this receptor and other transacting factor genes may confound physiological studies of regulation of target genes and will need to be considered in future human and animal studies. This approach to genetic analysis provides a paradigm for the study of functional variation in trans-acting factors and the role such variation may play in the generation and evolution of physiological diversity.</description><subject>1,25-dihydroxycholecalciferol</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Bone density</subject><subject>Bones</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Fraternal twins</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Genetic variation</subject><subject>Genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genotypes</subject><subject>Human</subject><subject>levels</subject><subject>man</subject><subject>Medical genetics</subject><subject>Medical research</subject><subject>osteocalcin</subject><subject>Proteins</subject><subject>Receptors</subject><subject>restriction fragment length polymorphism</subject><subject>trans-acting factor</subject><subject>Vitamin D</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><recordid>eNpdkElPHDEQhS2USExIzlw4WCjKrYfy0l64jYawSAgQIlxbpscNHrntju0-zN_IL45ZlENOpVJ99areQ-iQwJKAZCdTMHmp9JK0SyFEu4cWBDRpBNfwCS0AqGwUp3wffcl5CwC6VbBAf9YxlOSe5uJiwHHAD8mE3Kz64sIzPjd9iQmvvLfeZlwivolpNB7fveyyiz4-u752jyY58-S8K7tT_OiKGV3AZ_je9nZ63b-wweK76HdjTNOLy2PGJmzw2qV-9ubt0m0uNlat3oWv6PNgfLbfPuoB-nX-82F92VzfXlytV9fNlgpSqhm-sVQCs8aQjRqYGDglutWcUUklV1pLJVrKgFGhhaSEczIoa615xRg7QD_edacUf882l250ubfem2DjnDsiGBDGVQWP_wO3cU6h_tbRSkgJwCv0_QMyufoYaoy9y92U3GjSrmu5FABtxY7esW2uyfwbU9ZqxTX7Cy3vi00</recordid><startdate>19920801</startdate><enddate>19920801</enddate><creator>Morrison, Nigel A.</creator><creator>Yeoman, Rosanne</creator><creator>Kelly, Paul J.</creator><creator>Eisman, John A.</creator><general>National Academy of Sciences of the United States of America</general><general>National Academy of Sciences</general><scope>IQODW</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7T3</scope></search><sort><creationdate>19920801</creationdate><title>Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin</title><author>Morrison, Nigel A. ; Yeoman, Rosanne ; Kelly, Paul J. ; Eisman, John A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j261t-844de2703eaa1d8f36f4219594327274899786523032696721441f8eeea219533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>1,25-dihydroxycholecalciferol</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Bone density</topic><topic>Bones</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Fraternal twins</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes</topic><topic>Genetic variation</topic><topic>Genetics</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genotypes</topic><topic>Human</topic><topic>levels</topic><topic>man</topic><topic>Medical genetics</topic><topic>Medical research</topic><topic>osteocalcin</topic><topic>Proteins</topic><topic>Receptors</topic><topic>restriction fragment length polymorphism</topic><topic>trans-acting factor</topic><topic>Vitamin D</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morrison, Nigel A.</creatorcontrib><creatorcontrib>Yeoman, Rosanne</creatorcontrib><creatorcontrib>Kelly, Paul J.</creatorcontrib><creatorcontrib>Eisman, John A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Human Genome Abstracts</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morrison, Nigel A.</au><au>Yeoman, Rosanne</au><au>Kelly, Paul J.</au><au>Eisman, John A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><date>1992-08-01</date><risdate>1992</risdate><volume>89</volume><issue>15</issue><spage>6665</spage><epage>6669</epage><pages>6665-6669</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of bone turnover in normal and disease states. Its synthesis is induced by calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor and a specific vitamin D-responsive element in the osteocalcin gene promoter. Serum concentrations of osteocalcin are under strong genetic influence. To ascertain whether variability in circulating osteocalcin levels may reflect allelic variation in the vitamin D receptor gene, we have analyzed the relationship between frequent restriction fragment length polymorphisms (RFLPs, detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91 Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating osteocalcin levels (P $<$ 0.0001) independent of age or menopause effects. Since the osteocalcin gene and the vitamin D receptor gene are encoded on different chromosomes, the interaction between these two genes occurs in trans. Thus, common alleles of this trans-acting factor, the vitamin D receptor, are functionally different and contribute to "normal" physiological variability in osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs indicates that the greater diversity in lumbar spine density between the dizygotic pairs can be explained by divergence in vitamin D receptor alleles. Variations in this receptor and other transacting factor genes may confound physiological studies of regulation of target genes and will need to be considered in future human and animal studies. This approach to genetic analysis provides a paradigm for the study of functional variation in trans-acting factors and the role such variation may play in the generation and evolution of physiological diversity.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><doi>10.1073/pnas.89.15.6665</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (15), p.6665-6669 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16301348 |
| source | JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 1,25-dihydroxycholecalciferol Alleles Biological and medical sciences Bone density Bones Classical genetics, quantitative genetics, hybrids Fraternal twins Fundamental and applied biological sciences. Psychology Genes Genetic variation Genetics Genetics of eukaryotes. Biological and molecular evolution Genotypes Human levels man Medical genetics Medical research osteocalcin Proteins Receptors restriction fragment length polymorphism trans-acting factor Vitamin D |
| title | Contribution of Trans-Acting Factor Alleles to Normal Physiological Variability: Vitamin D Receptor Gene Polymorphisms and Circulating Osteocalcin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T14%3A21%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Contribution%20of%20Trans-Acting%20Factor%20Alleles%20to%20Normal%20Physiological%20Variability:%20Vitamin%20D%20Receptor%20Gene%20Polymorphisms%20and%20Circulating%20Osteocalcin&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Morrison,%20Nigel%20A.&rft.date=1992-08-01&rft.volume=89&rft.issue=15&rft.spage=6665&rft.epage=6669&rft.pages=6665-6669&rft.issn=0027-8424&rft.eissn=1091-6490&rft.coden=PNASA6&rft_id=info:doi/10.1073/pnas.89.15.6665&rft_dat=%3Cjstor_proqu%3E2359849%3C/jstor_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201377004&rft_id=info:pmid/&rft_jstor_id=2359849&rfr_iscdi=true |