Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population
Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome...
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| Veröffentlicht in: | Genetic testing and molecular biomarkers 2020-12, Vol.24 (12), p.789-797 |
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| creator | Huang, Ronglan Zhan, Qinghao Hu, Wenbin Yang, Renmin Cheng, Nan Han, Yongsheng Yue, Xiuyu |
| description | Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 (
), and the drug transporter gene, ATP-binding cassette subfamily B member 1 (
), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH.
In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the
gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus.
We found that the T allele of the
rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992,
= 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the
gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972,
= 0.042). The CpG sites with significant differences (
|
| doi_str_mv | 10.1089/gtmb.2020.0201 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7755856</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2471529983</sourcerecordid><originalsourceid>FETCH-LOGICAL-c418t-3c07fe7a633d0b008f17c9be88b38bd1aa2065232ffbccc7f0133b4137b423c23</originalsourceid><addsrcrecordid>eNpVkUtv1DAUhS0Eog_YskSWWGfwI46dDdI00IdUaCVgwcqyHadxNbEH26Ga_8MPxemUESwsX917_J0rHwDeYLTCSLTv7_KkVwQRtCoHPwPHuK1ZhQjjzw91w47ASUr3CDU1Fc1LcEQpYYQ07TH4vU4pGKeyCx6GAa7PujMMle9h9-O2ZgheWG_hbdjsphC3o0tTepzm0boIP35Zw882j7vNHvA1qzwn-ODyWGobg-urK9_PxvbwJmUbvDUxJJcWq4KA57Zg1QZeWtVD5x973ei8TYvpdt5zX4EXg9ok-_rpPgXfzz996y6r65uLq259XZkai1xRg_hguWoo7ZFGSAyYm1ZbITQVusdKEdQwQskwaGMMHxCmVNeYcl0Tagg9BR_23O2sJ9sb63NZTm6jm1TcyaCc_H_i3Sjvwi_JOWOCNQXw7gkQw8_Zpizvwxx92VmSmmNG2lbQolrtVctfpGiHgwNGcklVLqnKJVW5pFoevP13r4P8b4z0D9VboDs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2471529983</pqid></control><display><type>article</type><title>Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population</title><source>Alma/SFX Local Collection</source><creator>Huang, Ronglan ; Zhan, Qinghao ; Hu, Wenbin ; Yang, Renmin ; Cheng, Nan ; Han, Yongsheng ; Yue, Xiuyu</creator><creatorcontrib>Huang, Ronglan ; Zhan, Qinghao ; Hu, Wenbin ; Yang, Renmin ; Cheng, Nan ; Han, Yongsheng ; Yue, Xiuyu</creatorcontrib><description>Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 (
), and the drug transporter gene, ATP-binding cassette subfamily B member 1 (
), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH.
In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the
gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus.
We found that the T allele of the
rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992,
= 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the
gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972,
= 0.042). The CpG sites with significant differences (
< 0.05) in methylation levels between the cases and controls were
. A total of 14 pairs of linear regression tests between SNPs and methylation sites demonstrated statistical significance (
< 0.05).
This study provides evidence for two steroid-induced ONFH susceptibility genes (
,
) in the Han Chinese population.</description><identifier>ISSN: 1945-0265</identifier><identifier>EISSN: 1945-0257</identifier><identifier>DOI: 10.1089/gtmb.2020.0201</identifier><identifier>PMID: 33252269</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adenosine triphosphate ; Alleles ; Biomedical materials ; Confidence intervals ; CpG islands ; Cytochrome ; Cytochrome P450 ; Cytochromes P450 ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Etiology ; Femur ; Gene mapping ; Gene polymorphism ; Genes ; Genetic analysis ; Metabolism ; Nucleotides ; Original ; Osteonecrosis ; Pathogenesis ; Quantitative trait loci ; Regression analysis ; Risk management ; Risk reduction ; Single-nucleotide polymorphism ; Statistical analysis ; Statistics ; Steroid hormones ; Steroids</subject><ispartof>Genetic testing and molecular biomarkers, 2020-12, Vol.24 (12), p.789-797</ispartof><rights>Copyright Mary Ann Liebert, Inc. Dec 2020</rights><rights>Copyright 2020, Mary Ann Liebert, Inc., publishers 2020 Mary Ann Liebert, Inc., publishers</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-3c07fe7a633d0b008f17c9be88b38bd1aa2065232ffbccc7f0133b4137b423c23</citedby><cites>FETCH-LOGICAL-c418t-3c07fe7a633d0b008f17c9be88b38bd1aa2065232ffbccc7f0133b4137b423c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33252269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Ronglan</creatorcontrib><creatorcontrib>Zhan, Qinghao</creatorcontrib><creatorcontrib>Hu, Wenbin</creatorcontrib><creatorcontrib>Yang, Renmin</creatorcontrib><creatorcontrib>Cheng, Nan</creatorcontrib><creatorcontrib>Han, Yongsheng</creatorcontrib><creatorcontrib>Yue, Xiuyu</creatorcontrib><title>Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population</title><title>Genetic testing and molecular biomarkers</title><addtitle>Genet Test Mol Biomarkers</addtitle><description>Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 (
), and the drug transporter gene, ATP-binding cassette subfamily B member 1 (
), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH.
In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the
gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus.
We found that the T allele of the
rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992,
= 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the
gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972,
= 0.042). The CpG sites with significant differences (
< 0.05) in methylation levels between the cases and controls were
. A total of 14 pairs of linear regression tests between SNPs and methylation sites demonstrated statistical significance (
< 0.05).
This study provides evidence for two steroid-induced ONFH susceptibility genes (
,
) in the Han Chinese population.</description><subject>Adenosine triphosphate</subject><subject>Alleles</subject><subject>Biomedical materials</subject><subject>Confidence intervals</subject><subject>CpG islands</subject><subject>Cytochrome</subject><subject>Cytochrome P450</subject><subject>Cytochromes P450</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Etiology</subject><subject>Femur</subject><subject>Gene mapping</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic analysis</subject><subject>Metabolism</subject><subject>Nucleotides</subject><subject>Original</subject><subject>Osteonecrosis</subject><subject>Pathogenesis</subject><subject>Quantitative trait loci</subject><subject>Regression analysis</subject><subject>Risk management</subject><subject>Risk reduction</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Statistics</subject><subject>Steroid hormones</subject><subject>Steroids</subject><issn>1945-0265</issn><issn>1945-0257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpVkUtv1DAUhS0Eog_YskSWWGfwI46dDdI00IdUaCVgwcqyHadxNbEH26Ga_8MPxemUESwsX917_J0rHwDeYLTCSLTv7_KkVwQRtCoHPwPHuK1ZhQjjzw91w47ASUr3CDU1Fc1LcEQpYYQ07TH4vU4pGKeyCx6GAa7PujMMle9h9-O2ZgheWG_hbdjsphC3o0tTepzm0boIP35Zw882j7vNHvA1qzwn-ODyWGobg-urK9_PxvbwJmUbvDUxJJcWq4KA57Zg1QZeWtVD5x973ei8TYvpdt5zX4EXg9ok-_rpPgXfzz996y6r65uLq259XZkai1xRg_hguWoo7ZFGSAyYm1ZbITQVusdKEdQwQskwaGMMHxCmVNeYcl0Tagg9BR_23O2sJ9sb63NZTm6jm1TcyaCc_H_i3Sjvwi_JOWOCNQXw7gkQw8_Zpizvwxx92VmSmmNG2lbQolrtVctfpGiHgwNGcklVLqnKJVW5pFoevP13r4P8b4z0D9VboDs</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Huang, Ronglan</creator><creator>Zhan, Qinghao</creator><creator>Hu, Wenbin</creator><creator>Yang, Renmin</creator><creator>Cheng, Nan</creator><creator>Han, Yongsheng</creator><creator>Yue, Xiuyu</creator><general>Mary Ann Liebert, Inc</general><general>Mary Ann Liebert, Inc., publishers</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>202012</creationdate><title>Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population</title><author>Huang, Ronglan ; Zhan, Qinghao ; Hu, Wenbin ; Yang, Renmin ; Cheng, Nan ; Han, Yongsheng ; Yue, Xiuyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-3c07fe7a633d0b008f17c9be88b38bd1aa2065232ffbccc7f0133b4137b423c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenosine triphosphate</topic><topic>Alleles</topic><topic>Biomedical materials</topic><topic>Confidence intervals</topic><topic>CpG islands</topic><topic>Cytochrome</topic><topic>Cytochrome P450</topic><topic>Cytochromes P450</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Etiology</topic><topic>Femur</topic><topic>Gene mapping</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Genetic analysis</topic><topic>Metabolism</topic><topic>Nucleotides</topic><topic>Original</topic><topic>Osteonecrosis</topic><topic>Pathogenesis</topic><topic>Quantitative trait loci</topic><topic>Regression analysis</topic><topic>Risk management</topic><topic>Risk reduction</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>Statistics</topic><topic>Steroid hormones</topic><topic>Steroids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Ronglan</creatorcontrib><creatorcontrib>Zhan, Qinghao</creatorcontrib><creatorcontrib>Hu, Wenbin</creatorcontrib><creatorcontrib>Yang, Renmin</creatorcontrib><creatorcontrib>Cheng, Nan</creatorcontrib><creatorcontrib>Han, Yongsheng</creatorcontrib><creatorcontrib>Yue, Xiuyu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genetic testing and molecular biomarkers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Ronglan</au><au>Zhan, Qinghao</au><au>Hu, Wenbin</au><au>Yang, Renmin</au><au>Cheng, Nan</au><au>Han, Yongsheng</au><au>Yue, Xiuyu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population</atitle><jtitle>Genetic testing and molecular biomarkers</jtitle><addtitle>Genet Test Mol Biomarkers</addtitle><date>2020-12</date><risdate>2020</risdate><volume>24</volume><issue>12</issue><spage>789</spage><epage>797</epage><pages>789-797</pages><issn>1945-0265</issn><eissn>1945-0257</eissn><abstract>Osteonecrosis of the femoral head (ONFH) is a severe pathological state with multiple etiologies. Steroid hormone metabolism-related genes play an important role in ONFH. The aim of this study was to investigate the relationships between polymorphisms of the drug-metabolizing enzyme gene, cytochrome P450 (
), and the drug transporter gene, ATP-binding cassette subfamily B member 1 (
), as well as their DNA methylation status with the pathogenesis of steroid-induced ONFH.
In this case-control study, we evaluated five single nucleotide polymorphisms (SNPs) in two genes in a Han Chinese population, including 79 patients with steroid-induced ONFH and 114 persons who took steroids but did not develop steroid-induced ONFH. SNPs were genotyped by the improved multiplex ligation detection reaction. MethylTarget technology was used to ascertain the methylation status at two CpG islands in the
gene for statistical analysis. Finally, interactions between the SNPs and the CpG site's methylation levels were statistically analyzed by methylation quantitative trait locus.
We found that the T allele of the
rs2242480 locus was associated with steroid-induced ONFH risk reduction (odds ratio [OR] = 0.598, 95% confidence interval [CI]: 0.360-0.992,
= 0.046). In the genetic model analysis, the T allele of the rs2032582 locus in the
gene was associated with a reduced risk of steroid-induced ONFH under the dominant model (OR = 0.465, 95% CI: 0.223-0.972,
= 0.042). The CpG sites with significant differences (
< 0.05) in methylation levels between the cases and controls were
. A total of 14 pairs of linear regression tests between SNPs and methylation sites demonstrated statistical significance (
< 0.05).
This study provides evidence for two steroid-induced ONFH susceptibility genes (
,
) in the Han Chinese population.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>33252269</pmid><doi>10.1089/gtmb.2020.0201</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Genetic testing and molecular biomarkers, 2020-12, Vol.24 (12), p.789-797 |
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| language | eng |
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| source | Alma/SFX Local Collection |
| subjects | Adenosine triphosphate Alleles Biomedical materials Confidence intervals CpG islands Cytochrome Cytochrome P450 Cytochromes P450 Deoxyribonucleic acid DNA DNA methylation Etiology Femur Gene mapping Gene polymorphism Genes Genetic analysis Metabolism Nucleotides Original Osteonecrosis Pathogenesis Quantitative trait loci Regression analysis Risk management Risk reduction Single-nucleotide polymorphism Statistical analysis Statistics Steroid hormones Steroids |
| title | Association of ABCB1 and CYP450 Gene Polymorphisms and their DNA Methylation Status with Steroid-Induced Osteonecrosis of the Femoral Head in the Chinese Population |
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