CYP2C9 genotype and association with bone mineral density: A pilot study
In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop o...
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| Veröffentlicht in: | Gene 2013-09, Vol.526 (2), p.295-298 |
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| description | In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.
Ninety two consecutive angiologic outpatients, mean age: 60.3±14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.
59% of the patients (n=54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p=0.02).
Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.
The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.
•CYP2C9*2 and CYP2C9*3 influence the response to oral anticoagulant drugs.•Oral anticoagulant drugs are positively associated with the risk for osteoporosis.•CYP2C9 mutations are significantly associated with reduced BMD.•CYP2C9 polymorphisms–linked bone loss may be mediated via glucocorticoid synthesis. |
| doi_str_mv | 10.1016/j.gene.2013.05.026 |
| format | Article |
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Ninety two consecutive angiologic outpatients, mean age: 60.3±14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.
59% of the patients (n=54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p=0.02).
Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.
The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.
•CYP2C9*2 and CYP2C9*3 influence the response to oral anticoagulant drugs.•Oral anticoagulant drugs are positively associated with the risk for osteoporosis.•CYP2C9 mutations are significantly associated with reduced BMD.•CYP2C9 polymorphisms–linked bone loss may be mediated via glucocorticoid synthesis.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2013.05.026</identifier><identifier>PMID: 23732294</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Age Factors ; Aged ; anticoagulants ; Aryl Hydrocarbon Hydroxylases - genetics ; Australia ; Body Mass Index ; bone density ; Bone Density - genetics ; bone resorption ; CYP2C9 mutation ; cytochrome P-450 ; Cytochrome P-450 CYP2C9 ; dual-energy X-ray absorptiometry ; elderly ; Female ; femur ; genes ; Genetic Association Studies ; Genotype ; Glucocorticoid synthesis ; heterozygosity ; Humans ; lumbar spine ; Male ; Middle Aged ; Odds Ratio ; Oral anticoagulant treatment ; osteopenia ; Osteoporosis ; patients ; people ; Pilot Projects ; risk ; Sex Factors ; single nucleotide polymorphism</subject><ispartof>Gene, 2013-09, Vol.526 (2), p.295-298</ispartof><rights>2013 Elsevier B.V.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-6b1c94b0066d1489ba64fe13f438b66474e7f1cca4796059eab78b80ae941dc33</citedby><cites>FETCH-LOGICAL-c380t-6b1c94b0066d1489ba64fe13f438b66474e7f1cca4796059eab78b80ae941dc33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378111913006628$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23732294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brunner-Ziegler, Sophie</creatorcontrib><creatorcontrib>Giurgea, Georgiana-Aura</creatorcontrib><creatorcontrib>Sunder-Plassmann, Raute</creatorcontrib><creatorcontrib>Hammer, Alexandra</creatorcontrib><creatorcontrib>Margeta, Christian</creatorcontrib><creatorcontrib>Brunner, Martin</creatorcontrib><creatorcontrib>Koppensteiner, Renate</creatorcontrib><creatorcontrib>Mannhalter, Christine</creatorcontrib><title>CYP2C9 genotype and association with bone mineral density: A pilot study</title><title>Gene</title><addtitle>Gene</addtitle><description>In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.
Ninety two consecutive angiologic outpatients, mean age: 60.3±14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.
59% of the patients (n=54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p=0.02).
Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.
The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.
•CYP2C9*2 and CYP2C9*3 influence the response to oral anticoagulant drugs.•Oral anticoagulant drugs are positively associated with the risk for osteoporosis.•CYP2C9 mutations are significantly associated with reduced BMD.•CYP2C9 polymorphisms–linked bone loss may be mediated via glucocorticoid synthesis.</description><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>anticoagulants</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Australia</subject><subject>Body Mass Index</subject><subject>bone density</subject><subject>Bone Density - genetics</subject><subject>bone resorption</subject><subject>CYP2C9 mutation</subject><subject>cytochrome P-450</subject><subject>Cytochrome P-450 CYP2C9</subject><subject>dual-energy X-ray absorptiometry</subject><subject>elderly</subject><subject>Female</subject><subject>femur</subject><subject>genes</subject><subject>Genetic Association Studies</subject><subject>Genotype</subject><subject>Glucocorticoid synthesis</subject><subject>heterozygosity</subject><subject>Humans</subject><subject>lumbar spine</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Oral anticoagulant treatment</subject><subject>osteopenia</subject><subject>Osteoporosis</subject><subject>patients</subject><subject>people</subject><subject>Pilot Projects</subject><subject>risk</subject><subject>Sex Factors</subject><subject>single nucleotide polymorphism</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFO3DAQhi3UqmxpX4BD8ZFLgsd2nBj1gla0ICGBBBx6shxnQr3KxlvbS7VvX6-W9ti5zOX7_xl9hJwCq4GBuljVLzhjzRmImjU14-qILKBrdcWY6N6RBRNtVwGAPiYfU1qxMk3DP5BjLlrBuZYLcrP88cCXmpamkHcbpHYeqE0pOG-zDzP97fNP2ocZ6drPGO1EB5yTz7tLekU3fgqZprwddp_I-9FOCT-_7RPy_O36aXlT3d1_v11e3VVOdCxXqgenZc-YUgPITvdWyRFBjFJ0vVKyldiO4JyVrVas0Wj7tus7ZlFLGJwQJ-T80LuJ4dcWUzZrnxxOk50xbJMBCY1iQmkoKD-gLoaUIo5mE_3axp0BZvYGzcrsDZq9QcMaUwyW0Je3_m2_xuFf5K-yApwdgNEGY1-iT-b5sTQ0xa6Uiu_vfj0QWDy8eowmOY-zw8FHdNkMwf_vgz-CfImN</recordid><startdate>20130910</startdate><enddate>20130910</enddate><creator>Brunner-Ziegler, Sophie</creator><creator>Giurgea, Georgiana-Aura</creator><creator>Sunder-Plassmann, Raute</creator><creator>Hammer, Alexandra</creator><creator>Margeta, Christian</creator><creator>Brunner, Martin</creator><creator>Koppensteiner, Renate</creator><creator>Mannhalter, Christine</creator><general>Elsevier B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130910</creationdate><title>CYP2C9 genotype and association with bone mineral density: A pilot study</title><author>Brunner-Ziegler, Sophie ; Giurgea, Georgiana-Aura ; Sunder-Plassmann, Raute ; Hammer, Alexandra ; Margeta, Christian ; Brunner, Martin ; Koppensteiner, Renate ; Mannhalter, Christine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-6b1c94b0066d1489ba64fe13f438b66474e7f1cca4796059eab78b80ae941dc33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>anticoagulants</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Australia</topic><topic>Body Mass Index</topic><topic>bone density</topic><topic>Bone Density - genetics</topic><topic>bone resorption</topic><topic>CYP2C9 mutation</topic><topic>cytochrome P-450</topic><topic>Cytochrome P-450 CYP2C9</topic><topic>dual-energy X-ray absorptiometry</topic><topic>elderly</topic><topic>Female</topic><topic>femur</topic><topic>genes</topic><topic>Genetic Association Studies</topic><topic>Genotype</topic><topic>Glucocorticoid synthesis</topic><topic>heterozygosity</topic><topic>Humans</topic><topic>lumbar spine</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Odds Ratio</topic><topic>Oral anticoagulant treatment</topic><topic>osteopenia</topic><topic>Osteoporosis</topic><topic>patients</topic><topic>people</topic><topic>Pilot Projects</topic><topic>risk</topic><topic>Sex Factors</topic><topic>single nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brunner-Ziegler, Sophie</creatorcontrib><creatorcontrib>Giurgea, Georgiana-Aura</creatorcontrib><creatorcontrib>Sunder-Plassmann, Raute</creatorcontrib><creatorcontrib>Hammer, Alexandra</creatorcontrib><creatorcontrib>Margeta, Christian</creatorcontrib><creatorcontrib>Brunner, Martin</creatorcontrib><creatorcontrib>Koppensteiner, Renate</creatorcontrib><creatorcontrib>Mannhalter, Christine</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brunner-Ziegler, Sophie</au><au>Giurgea, Georgiana-Aura</au><au>Sunder-Plassmann, Raute</au><au>Hammer, Alexandra</au><au>Margeta, Christian</au><au>Brunner, Martin</au><au>Koppensteiner, Renate</au><au>Mannhalter, Christine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CYP2C9 genotype and association with bone mineral density: A pilot study</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2013-09-10</date><risdate>2013</risdate><volume>526</volume><issue>2</issue><spage>295</spage><epage>298</epage><pages>295-298</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.
Ninety two consecutive angiologic outpatients, mean age: 60.3±14.4, without secondary causes of bone loss were genotyped and classified as patients with normal BMD, osteopenia and osteoporosis according to WHO criteria by dual-energy X-ray absorptiometry at the lumbar spine and/or the femoral neck. Potential association between the CYP2C9 genotype and BMD was tested.
59% of the patients (n=54) presented with reduced BMD and were compared to 38 age-matched persons with normal BMD. The genotype distribution showed 15% heterozygous for CYP2C9*2 p.Arg144Cys, 14% for CYP2C9*3 p.IIe359Leu, 2% for both polymorphisms, and 69% had wildtype genotypes. Patients with CYP2C9 mutations had significantly lower BMD values at the femoral neck and displayed a four-fold higher adjusted risk to suffer from reduced BMD than individuals with wildtype genotypes (p=0.02).
Oral anticoagulant treatment is common in angiologic outpatients. The gene variants CYP2C9*2 and CYP2C9*3 have been shown to require lower maintenance doses of oral anticoagulant drugs. An association between oral anticoagulant drugs and the susceptibility to develop osteoporosis in relation to sequence variations in the CYP2C9 gene is suggested to be mediated via the glucocorticoid synthesis pathway.
The CYP2C9*2/CYP2C9*3 variants were significantly associated with femoral BMD in a selected elderly Austrian population. These variants could contribute to the complex risk to develop osteoporosis.
•CYP2C9*2 and CYP2C9*3 influence the response to oral anticoagulant drugs.•Oral anticoagulant drugs are positively associated with the risk for osteoporosis.•CYP2C9 mutations are significantly associated with reduced BMD.•CYP2C9 polymorphisms–linked bone loss may be mediated via glucocorticoid synthesis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23732294</pmid><doi>10.1016/j.gene.2013.05.026</doi><tpages>4</tpages></addata></record> |
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| subjects | Adult Age Factors Aged anticoagulants Aryl Hydrocarbon Hydroxylases - genetics Australia Body Mass Index bone density Bone Density - genetics bone resorption CYP2C9 mutation cytochrome P-450 Cytochrome P-450 CYP2C9 dual-energy X-ray absorptiometry elderly Female femur genes Genetic Association Studies Genotype Glucocorticoid synthesis heterozygosity Humans lumbar spine Male Middle Aged Odds Ratio Oral anticoagulant treatment osteopenia Osteoporosis patients people Pilot Projects risk Sex Factors single nucleotide polymorphism |
| title | CYP2C9 genotype and association with bone mineral density: A pilot study |
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