Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease
The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were se...
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| Veröffentlicht in: | ENDOCRINE JOURNAL 2016, Vol.63(7), pp.643-653 |
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| creator | Cai, Tian-tian Zhang, Jian Wang, Xuan Song, Rong-hua Qin, Qiu Muhali, Fatuma-said Zhou, Jiao-zhen Xu, Jian Zhang, Jin-an |
| description | The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves’ disease (GD) patients, 353 Hashimoto’s thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD. |
| doi_str_mv | 10.1507/endocrj.EJ15-0596 |
| format | Article |
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Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves’ disease (GD) patients, 353 Hashimoto’s thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.</description><identifier>ISSN: 0918-8959</identifier><identifier>EISSN: 1348-4540</identifier><identifier>DOI: 10.1507/endocrj.EJ15-0596</identifier><identifier>PMID: 27237591</identifier><language>eng</language><publisher>Japan: The Japan Endocrine Society</publisher><subject>Adult ; Autoimmune thyroid diseases ; Case-Control Studies ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA Methylation ; DNA Methyltransferase 3A ; DNA Methyltransferase 3B ; DNA methyltransferases (DNMTs) ; Epistasis, Genetic ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Graves Disease - genetics ; Graves’ disease ; Hashimoto’s thyroiditis ; Humans ; Male ; Polymorphism, Single Nucleotide ; Sex Factors ; Single nucleotide polymorphism (SNP) ; Thyroiditis, Autoimmune - genetics</subject><ispartof>Endocrine Journal, 2016, Vol.63(7), pp.643-653</ispartof><rights>The Japan Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c663t-b931fe87f6cac2d3cd081076555cb13f2de5e635a7ee51c3937853417c83b39c3</citedby><cites>FETCH-LOGICAL-c663t-b931fe87f6cac2d3cd081076555cb13f2de5e635a7ee51c3937853417c83b39c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1884,4025,27925,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27237591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Tian-tian</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Song, Rong-hua</creatorcontrib><creatorcontrib>Qin, Qiu</creatorcontrib><creatorcontrib>Muhali, Fatuma-said</creatorcontrib><creatorcontrib>Zhou, Jiao-zhen</creatorcontrib><creatorcontrib>Xu, Jian</creatorcontrib><creatorcontrib>Zhang, Jin-an</creatorcontrib><creatorcontrib>Clinical Laboratory</creatorcontrib><creatorcontrib>Department of Endocrinology</creatorcontrib><creatorcontrib>Jinshan Hospital of Fudan University</creatorcontrib><title>Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease</title><title>ENDOCRINE JOURNAL</title><addtitle>Endocr J</addtitle><description>The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves’ disease (GD) patients, 353 Hashimoto’s thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.</description><subject>Adult</subject><subject>Autoimmune thyroid diseases</subject><subject>Case-Control Studies</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA Methylation</subject><subject>DNA Methyltransferase 3A</subject><subject>DNA Methyltransferase 3B</subject><subject>DNA methyltransferases (DNMTs)</subject><subject>Epistasis, Genetic</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Graves Disease - genetics</subject><subject>Graves’ disease</subject><subject>Hashimoto’s thyroiditis</subject><subject>Humans</subject><subject>Male</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Sex Factors</subject><subject>Single nucleotide polymorphism (SNP)</subject><subject>Thyroiditis, Autoimmune - genetics</subject><issn>0918-8959</issn><issn>1348-4540</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkU1v1DAQhi0EokvhB3BBOXJoip2JP3IspSygtlzK2fI6k61Xib21E4n--zq7S8TB45H8zDvjdwj5yOgl41R-Qd8GG3eXN78YLylvxCuyYlCrsuY1fU1WtGGqVA1vzsi7lHaUAvAa3pKzSlYgecNWZLtGj-U2h8L4tpiTMuHfAvcujWZ0tnB-xGjs6IJPReiKb_d3D-zicMHVoeiQfs1gYaYxuGGYstr4-ByDa4vWJTQJ35M3nekTfjjd5-TP95uH6x_l7e_1z-ur29IKAWO5aYB1qGQnrLFVC7alilEpOOd2w6CrWuQogBuJyJmFBqTiUDNpFWygsXBOPh919zE8TZhGPbhkse-NxzAlzRRVoISsaEbZEbUxpBSx0_voBhOfNaN69lef_NWzv3r2N9d8OslPmwHbpeKfoRlYH4H86qzpg--dR70LU_T539o-iYOqrigTmlIBuQ-dj6ghBw6VpEKw_5R2eRFbXFqZmLfS4zKcAC3nsAy5EPbRxIzBC4EkprE</recordid><startdate>2016</startdate><enddate>2016</enddate><creator>Cai, Tian-tian</creator><creator>Zhang, Jian</creator><creator>Wang, Xuan</creator><creator>Song, Rong-hua</creator><creator>Qin, Qiu</creator><creator>Muhali, Fatuma-said</creator><creator>Zhou, Jiao-zhen</creator><creator>Xu, Jian</creator><creator>Zhang, Jin-an</creator><general>The Japan Endocrine Society</general><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>2016</creationdate><title>Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease</title><author>Cai, Tian-tian ; Zhang, Jian ; Wang, Xuan ; Song, Rong-hua ; Qin, Qiu ; Muhali, Fatuma-said ; Zhou, Jiao-zhen ; Xu, Jian ; Zhang, Jin-an</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c663t-b931fe87f6cac2d3cd081076555cb13f2de5e635a7ee51c3937853417c83b39c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Autoimmune thyroid diseases</topic><topic>Case-Control Studies</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA Methylation</topic><topic>DNA Methyltransferase 3A</topic><topic>DNA Methyltransferase 3B</topic><topic>DNA methyltransferases (DNMTs)</topic><topic>Epistasis, Genetic</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Graves Disease - genetics</topic><topic>Graves’ disease</topic><topic>Hashimoto’s thyroiditis</topic><topic>Humans</topic><topic>Male</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Sex Factors</topic><topic>Single nucleotide polymorphism (SNP)</topic><topic>Thyroiditis, Autoimmune - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Tian-tian</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Song, Rong-hua</creatorcontrib><creatorcontrib>Qin, Qiu</creatorcontrib><creatorcontrib>Muhali, Fatuma-said</creatorcontrib><creatorcontrib>Zhou, Jiao-zhen</creatorcontrib><creatorcontrib>Xu, Jian</creatorcontrib><creatorcontrib>Zhang, Jin-an</creatorcontrib><creatorcontrib>Clinical Laboratory</creatorcontrib><creatorcontrib>Department of Endocrinology</creatorcontrib><creatorcontrib>Jinshan Hospital of Fudan University</creatorcontrib><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>ENDOCRINE JOURNAL</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Tian-tian</au><au>Zhang, Jian</au><au>Wang, Xuan</au><au>Song, Rong-hua</au><au>Qin, Qiu</au><au>Muhali, Fatuma-said</au><au>Zhou, Jiao-zhen</au><au>Xu, Jian</au><au>Zhang, Jin-an</au><aucorp>Clinical Laboratory</aucorp><aucorp>Department of Endocrinology</aucorp><aucorp>Jinshan Hospital of Fudan University</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease</atitle><jtitle>ENDOCRINE JOURNAL</jtitle><addtitle>Endocr J</addtitle><date>2016</date><risdate>2016</risdate><volume>63</volume><issue>7</issue><spage>643</spage><epage>653</epage><pages>643-653</pages><issn>0918-8959</issn><eissn>1348-4540</eissn><abstract>The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves’ disease (GD) patients, 353 Hashimoto’s thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.</abstract><cop>Japan</cop><pub>The Japan Endocrine Society</pub><pmid>27237591</pmid><doi>10.1507/endocrj.EJ15-0596</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Endocrine Journal, 2016, Vol.63(7), pp.643-653 |
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| subjects | Adult Autoimmune thyroid diseases Case-Control Studies DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases - genetics DNA Methylation DNA Methyltransferase 3A DNA Methyltransferase 3B DNA methyltransferases (DNMTs) Epistasis, Genetic Female Gene Frequency Genetic Association Studies Genetic Predisposition to Disease Graves Disease - genetics Graves’ disease Hashimoto’s thyroiditis Humans Male Polymorphism, Single Nucleotide Sex Factors Single nucleotide polymorphism (SNP) Thyroiditis, Autoimmune - genetics |
| title | Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease |
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