Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population
The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with...
Gespeichert in:
| Veröffentlicht in: | Genes 2023-09, Vol.14 (9), p.1805 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 9 |
| container_start_page | 1805 |
| container_title | Genes |
| container_volume | 14 |
| creator | Kolb, Kathleen Liedtke Mira, Ana Luiza Sprotte Auer, Eduardo Delabio Bucco, Isabela Dall’Oglio de Lima e Silva, Carla Eduarda dos Santos, Priscila Ianzen Hoch, Valéria Bumiller-Bini Oliveira, Luana Caroline Hauser, Aline Borsato Hundt, Jennifer Elisabeth Shuldiner, Alan R Lopes, Fabiana Leão Boysen, Teide-Jens Franke, Andre Pinto, Luis Felipe Ribeiro Soares-Lima, Sheila Coelho Kretzschmar, Gabriela Canalli Boldt, Angelica Beate Winter |
| description | The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression. |
| doi_str_mv | 10.3390/genes14091805 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10530687</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A779737336</galeid><sourcerecordid>A779737336</sourcerecordid><originalsourceid>FETCH-LOGICAL-c460t-5a13386f7bf4521ad9cb8a9fe194869c15eaee3fced47aeb812ac092029fac013</originalsourceid><addsrcrecordid>eNptks9rHCEUgIfSQkOaY-9CL-lh0qfOjGMvJSztNpD-IG3P4jjPXcOMTtQp7H9fQ0LJlurBp37vezy0ql5TuOBcwrsdeky0AUl7aJ9VJwwEr5uGtc-fxC-rs5RuoYwGGEB7Ut1tp9UEE2J2JriR3KDBJYdItsVHzr_e8A19S76H6TCHuOxdmhPRfiRfMOshTM6QHwc_xjDje3Llk9vtcyK27EneY6G8D95lLIZlnXR2wb-qXlg9JTx7XE-rX58-_tx8rq-_ba82l9e1aTrIdasp531nxWCbllE9SjP0Wlqksuk7aWiLGpFbg2MjNA49ZdqAZMCkLQHlp9WHB--yDjOOBn2OelJLdLOOBxW0U8c33u3VLvxWFFoOXS-K4fzREMPdiimr2SWD06Q9hjUp1otSpwdgBX3zD3ob1uhLf4XqJGcCuifUTk-onLehFDb3UnUphBRccN4V6uI_VJkjzuWRPFpXzo8S6ocEE0NKEe3fJimo-8-hjj4H_wPiuK2t</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2869327062</pqid></control><display><type>article</type><title>Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Kolb, Kathleen Liedtke ; Mira, Ana Luiza Sprotte ; Auer, Eduardo Delabio ; Bucco, Isabela Dall’Oglio ; de Lima e Silva, Carla Eduarda ; dos Santos, Priscila Ianzen ; Hoch, Valéria Bumiller-Bini ; Oliveira, Luana Caroline ; Hauser, Aline Borsato ; Hundt, Jennifer Elisabeth ; Shuldiner, Alan R ; Lopes, Fabiana Leão ; Boysen, Teide-Jens ; Franke, Andre ; Pinto, Luis Felipe Ribeiro ; Soares-Lima, Sheila Coelho ; Kretzschmar, Gabriela Canalli ; Boldt, Angelica Beate Winter</creator><creatorcontrib>Kolb, Kathleen Liedtke ; Mira, Ana Luiza Sprotte ; Auer, Eduardo Delabio ; Bucco, Isabela Dall’Oglio ; de Lima e Silva, Carla Eduarda ; dos Santos, Priscila Ianzen ; Hoch, Valéria Bumiller-Bini ; Oliveira, Luana Caroline ; Hauser, Aline Borsato ; Hundt, Jennifer Elisabeth ; Shuldiner, Alan R ; Lopes, Fabiana Leão ; Boysen, Teide-Jens ; Franke, Andre ; Pinto, Luis Felipe Ribeiro ; Soares-Lima, Sheila Coelho ; Kretzschmar, Gabriela Canalli ; Boldt, Angelica Beate Winter</creatorcontrib><description>The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes14091805</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Blood pressure ; Body mass index ; Children ; Corticosteroids ; CpG islands ; Demographics ; Disease ; DNA methylation ; Ethylenediaminetetraacetic acid ; Exercise ; Feedback ; Gene expression ; Genes ; Genetic aspects ; Genetic polymorphisms ; Glucocorticoid receptors ; Glucocorticoids ; Glucose ; Haplotypes ; Hormones ; Hypertension ; Hypothalamic-pituitary-adrenal axis ; Hypothalamus ; Insulin resistance ; Investigations ; Mass spectroscopy ; Metabolic syndrome ; Methylation ; Obesity ; Physical activity ; Pituitary ; Pituitary gland ; Population ; Questionnaires ; Religious persecution</subject><ispartof>Genes, 2023-09, Vol.14 (9), p.1805</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-5a13386f7bf4521ad9cb8a9fe194869c15eaee3fced47aeb812ac092029fac013</citedby><cites>FETCH-LOGICAL-c460t-5a13386f7bf4521ad9cb8a9fe194869c15eaee3fced47aeb812ac092029fac013</cites><orcidid>0000-0003-4000-2417 ; 0009-0005-3152-1110 ; 0000-0002-0539-7612 ; 0000-0002-9147-5719 ; 0000-0002-6742-3708 ; 0000-0002-5357-242X ; 0000-0002-6639-8467</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530687/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530687/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Kolb, Kathleen Liedtke</creatorcontrib><creatorcontrib>Mira, Ana Luiza Sprotte</creatorcontrib><creatorcontrib>Auer, Eduardo Delabio</creatorcontrib><creatorcontrib>Bucco, Isabela Dall’Oglio</creatorcontrib><creatorcontrib>de Lima e Silva, Carla Eduarda</creatorcontrib><creatorcontrib>dos Santos, Priscila Ianzen</creatorcontrib><creatorcontrib>Hoch, Valéria Bumiller-Bini</creatorcontrib><creatorcontrib>Oliveira, Luana Caroline</creatorcontrib><creatorcontrib>Hauser, Aline Borsato</creatorcontrib><creatorcontrib>Hundt, Jennifer Elisabeth</creatorcontrib><creatorcontrib>Shuldiner, Alan R</creatorcontrib><creatorcontrib>Lopes, Fabiana Leão</creatorcontrib><creatorcontrib>Boysen, Teide-Jens</creatorcontrib><creatorcontrib>Franke, Andre</creatorcontrib><creatorcontrib>Pinto, Luis Felipe Ribeiro</creatorcontrib><creatorcontrib>Soares-Lima, Sheila Coelho</creatorcontrib><creatorcontrib>Kretzschmar, Gabriela Canalli</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><title>Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population</title><title>Genes</title><description>The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.</description><subject>Blood pressure</subject><subject>Body mass index</subject><subject>Children</subject><subject>Corticosteroids</subject><subject>CpG islands</subject><subject>Demographics</subject><subject>Disease</subject><subject>DNA methylation</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Exercise</subject><subject>Feedback</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Glucocorticoid receptors</subject><subject>Glucocorticoids</subject><subject>Glucose</subject><subject>Haplotypes</subject><subject>Hormones</subject><subject>Hypertension</subject><subject>Hypothalamic-pituitary-adrenal axis</subject><subject>Hypothalamus</subject><subject>Insulin resistance</subject><subject>Investigations</subject><subject>Mass spectroscopy</subject><subject>Metabolic syndrome</subject><subject>Methylation</subject><subject>Obesity</subject><subject>Physical activity</subject><subject>Pituitary</subject><subject>Pituitary gland</subject><subject>Population</subject><subject>Questionnaires</subject><subject>Religious persecution</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNptks9rHCEUgIfSQkOaY-9CL-lh0qfOjGMvJSztNpD-IG3P4jjPXcOMTtQp7H9fQ0LJlurBp37vezy0ql5TuOBcwrsdeky0AUl7aJ9VJwwEr5uGtc-fxC-rs5RuoYwGGEB7Ut1tp9UEE2J2JriR3KDBJYdItsVHzr_e8A19S76H6TCHuOxdmhPRfiRfMOshTM6QHwc_xjDje3Llk9vtcyK27EneY6G8D95lLIZlnXR2wb-qXlg9JTx7XE-rX58-_tx8rq-_ba82l9e1aTrIdasp531nxWCbllE9SjP0Wlqksuk7aWiLGpFbg2MjNA49ZdqAZMCkLQHlp9WHB--yDjOOBn2OelJLdLOOBxW0U8c33u3VLvxWFFoOXS-K4fzREMPdiimr2SWD06Q9hjUp1otSpwdgBX3zD3ob1uhLf4XqJGcCuifUTk-onLehFDb3UnUphBRccN4V6uI_VJkjzuWRPFpXzo8S6ocEE0NKEe3fJimo-8-hjj4H_wPiuK2t</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>Kolb, Kathleen Liedtke</creator><creator>Mira, Ana Luiza Sprotte</creator><creator>Auer, Eduardo Delabio</creator><creator>Bucco, Isabela Dall’Oglio</creator><creator>de Lima e Silva, Carla Eduarda</creator><creator>dos Santos, Priscila Ianzen</creator><creator>Hoch, Valéria Bumiller-Bini</creator><creator>Oliveira, Luana Caroline</creator><creator>Hauser, Aline Borsato</creator><creator>Hundt, Jennifer Elisabeth</creator><creator>Shuldiner, Alan R</creator><creator>Lopes, Fabiana Leão</creator><creator>Boysen, Teide-Jens</creator><creator>Franke, Andre</creator><creator>Pinto, Luis Felipe Ribeiro</creator><creator>Soares-Lima, Sheila Coelho</creator><creator>Kretzschmar, Gabriela Canalli</creator><creator>Boldt, Angelica Beate Winter</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4000-2417</orcidid><orcidid>https://orcid.org/0009-0005-3152-1110</orcidid><orcidid>https://orcid.org/0000-0002-0539-7612</orcidid><orcidid>https://orcid.org/0000-0002-9147-5719</orcidid><orcidid>https://orcid.org/0000-0002-6742-3708</orcidid><orcidid>https://orcid.org/0000-0002-5357-242X</orcidid><orcidid>https://orcid.org/0000-0002-6639-8467</orcidid></search><sort><creationdate>20230901</creationdate><title>Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population</title><author>Kolb, Kathleen Liedtke ; Mira, Ana Luiza Sprotte ; Auer, Eduardo Delabio ; Bucco, Isabela Dall’Oglio ; de Lima e Silva, Carla Eduarda ; dos Santos, Priscila Ianzen ; Hoch, Valéria Bumiller-Bini ; Oliveira, Luana Caroline ; Hauser, Aline Borsato ; Hundt, Jennifer Elisabeth ; Shuldiner, Alan R ; Lopes, Fabiana Leão ; Boysen, Teide-Jens ; Franke, Andre ; Pinto, Luis Felipe Ribeiro ; Soares-Lima, Sheila Coelho ; Kretzschmar, Gabriela Canalli ; Boldt, Angelica Beate Winter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-5a13386f7bf4521ad9cb8a9fe194869c15eaee3fced47aeb812ac092029fac013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Blood pressure</topic><topic>Body mass index</topic><topic>Children</topic><topic>Corticosteroids</topic><topic>CpG islands</topic><topic>Demographics</topic><topic>Disease</topic><topic>DNA methylation</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Exercise</topic><topic>Feedback</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Glucocorticoid receptors</topic><topic>Glucocorticoids</topic><topic>Glucose</topic><topic>Haplotypes</topic><topic>Hormones</topic><topic>Hypertension</topic><topic>Hypothalamic-pituitary-adrenal axis</topic><topic>Hypothalamus</topic><topic>Insulin resistance</topic><topic>Investigations</topic><topic>Mass spectroscopy</topic><topic>Metabolic syndrome</topic><topic>Methylation</topic><topic>Obesity</topic><topic>Physical activity</topic><topic>Pituitary</topic><topic>Pituitary gland</topic><topic>Population</topic><topic>Questionnaires</topic><topic>Religious persecution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kolb, Kathleen Liedtke</creatorcontrib><creatorcontrib>Mira, Ana Luiza Sprotte</creatorcontrib><creatorcontrib>Auer, Eduardo Delabio</creatorcontrib><creatorcontrib>Bucco, Isabela Dall’Oglio</creatorcontrib><creatorcontrib>de Lima e Silva, Carla Eduarda</creatorcontrib><creatorcontrib>dos Santos, Priscila Ianzen</creatorcontrib><creatorcontrib>Hoch, Valéria Bumiller-Bini</creatorcontrib><creatorcontrib>Oliveira, Luana Caroline</creatorcontrib><creatorcontrib>Hauser, Aline Borsato</creatorcontrib><creatorcontrib>Hundt, Jennifer Elisabeth</creatorcontrib><creatorcontrib>Shuldiner, Alan R</creatorcontrib><creatorcontrib>Lopes, Fabiana Leão</creatorcontrib><creatorcontrib>Boysen, Teide-Jens</creatorcontrib><creatorcontrib>Franke, Andre</creatorcontrib><creatorcontrib>Pinto, Luis Felipe Ribeiro</creatorcontrib><creatorcontrib>Soares-Lima, Sheila Coelho</creatorcontrib><creatorcontrib>Kretzschmar, Gabriela Canalli</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kolb, Kathleen Liedtke</au><au>Mira, Ana Luiza Sprotte</au><au>Auer, Eduardo Delabio</au><au>Bucco, Isabela Dall’Oglio</au><au>de Lima e Silva, Carla Eduarda</au><au>dos Santos, Priscila Ianzen</au><au>Hoch, Valéria Bumiller-Bini</au><au>Oliveira, Luana Caroline</au><au>Hauser, Aline Borsato</au><au>Hundt, Jennifer Elisabeth</au><au>Shuldiner, Alan R</au><au>Lopes, Fabiana Leão</au><au>Boysen, Teide-Jens</au><au>Franke, Andre</au><au>Pinto, Luis Felipe Ribeiro</au><au>Soares-Lima, Sheila Coelho</au><au>Kretzschmar, Gabriela Canalli</au><au>Boldt, Angelica Beate Winter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population</atitle><jtitle>Genes</jtitle><date>2023-09-01</date><risdate>2023</risdate><volume>14</volume><issue>9</issue><spage>1805</spage><pages>1805-</pages><issn>2073-4425</issn><eissn>2073-4425</eissn><abstract>The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/genes14091805</doi><orcidid>https://orcid.org/0000-0003-4000-2417</orcidid><orcidid>https://orcid.org/0009-0005-3152-1110</orcidid><orcidid>https://orcid.org/0000-0002-0539-7612</orcidid><orcidid>https://orcid.org/0000-0002-9147-5719</orcidid><orcidid>https://orcid.org/0000-0002-6742-3708</orcidid><orcidid>https://orcid.org/0000-0002-5357-242X</orcidid><orcidid>https://orcid.org/0000-0002-6639-8467</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2073-4425 |
| ispartof | Genes, 2023-09, Vol.14 (9), p.1805 |
| issn | 2073-4425 2073-4425 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10530687 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Blood pressure Body mass index Children Corticosteroids CpG islands Demographics Disease DNA methylation Ethylenediaminetetraacetic acid Exercise Feedback Gene expression Genes Genetic aspects Genetic polymorphisms Glucocorticoid receptors Glucocorticoids Glucose Haplotypes Hormones Hypertension Hypothalamic-pituitary-adrenal axis Hypothalamus Insulin resistance Investigations Mass spectroscopy Metabolic syndrome Methylation Obesity Physical activity Pituitary Pituitary gland Population Questionnaires Religious persecution |
| title | Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T02%3A57%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glucocorticoid%20Receptor%20Gene%20(NR3C1)%20Polymorphisms%20and%20Metabolic%20Syndrome:%20Insights%20from%20the%20Mennonite%20Population&rft.jtitle=Genes&rft.au=Kolb,%20Kathleen%20Liedtke&rft.date=2023-09-01&rft.volume=14&rft.issue=9&rft.spage=1805&rft.pages=1805-&rft.issn=2073-4425&rft.eissn=2073-4425&rft_id=info:doi/10.3390/genes14091805&rft_dat=%3Cgale_pubme%3EA779737336%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2869327062&rft_id=info:pmid/&rft_galeid=A779737336&rfr_iscdi=true |