Glucocorticoid Receptor Gene (<i>NR3C1</i>) 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 (<i>NR3C1</i>) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/14/9/1805 |
| _version_ | 1797579857730732032 |
|---|---|
| author | Kathleen Liedtke Kolb Ana Luiza Sprotte Mira Eduardo Delabio Auer Isabela Dall’Oglio Bucco Carla Eduarda de Lima e Silva Priscila Ianzen dos Santos Valéria Bumiller-Bini Hoch Luana Caroline Oliveira Aline Borsato Hauser Jennifer Elisabeth Hundt Alan R. Shuldiner Fabiana Leão Lopes Teide-Jens Boysen Andre Franke Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima Gabriela Canalli Kretzschmar Angelica Beate Winter Boldt |
| author_facet | Kathleen Liedtke Kolb Ana Luiza Sprotte Mira Eduardo Delabio Auer Isabela Dall’Oglio Bucco Carla Eduarda de Lima e Silva Priscila Ianzen dos Santos Valéria Bumiller-Bini Hoch Luana Caroline Oliveira Aline Borsato Hauser Jennifer Elisabeth Hundt Alan R. Shuldiner Fabiana Leão Lopes Teide-Jens Boysen Andre Franke Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima Gabriela Canalli Kretzschmar Angelica Beate Winter Boldt |
| author_sort | Kathleen Liedtke Kolb |
| collection | DOAJ |
| description | The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (<i>NR3C1</i>) 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 <i>NR3C1</i> in the genetically isolated Brazilian Mennonite population, we genotyped 20 <i>NR3C1</i> 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 <i>NR3C1</i> 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 <i>rs10482605*C</i> (OR = 4.74, <i>p</i>corr = 0.024) and the haplotype containing <i>TTCGTTGATT</i> (<i>rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T</i>, OR = 4.74, <i>p</i>corr = 0.048), as well as for the <i>CCT</i> haplotype (<i>rs41423247*C_ rs6877893*C_rs258763*T</i>), OR = 6.02, <i>p</i>corr = 0.030), but not to the differences in methylation or gene expression. Thus, <i>NR3C1</i> 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. |
| first_indexed | 2024-03-10T22:43:00Z |
| format | Article |
| id | doaj.art-0d794d3907654b76ba7f833aa6692391 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:00Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-0d794d3907654b76ba7f833aa66923912023-11-19T10:53:57ZengMDPI AGGenes2073-44252023-09-01149180510.3390/genes14091805Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite PopulationKathleen Liedtke Kolb0Ana Luiza Sprotte Mira1Eduardo Delabio Auer2Isabela Dall’Oglio Bucco3Carla Eduarda de Lima e Silva4Priscila Ianzen dos Santos5Valéria Bumiller-Bini Hoch6Luana Caroline Oliveira7Aline Borsato Hauser8Jennifer Elisabeth Hundt9Alan R. Shuldiner10Fabiana Leão Lopes11Teide-Jens Boysen12Andre Franke13Luis Felipe Ribeiro Pinto14Sheila Coelho Soares-Lima15Gabriela Canalli Kretzschmar16Angelica Beate Winter Boldt17Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory School of Clinical Analysis, Department of Pharmacy, Federal University of Paraná (UFPR), Av. Pref. Lothário Meissner, 632, Jardim Botânico, Curitiba 80210-170, PR, BrazilLübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee, 160, Haus 32, 23562 Lübeck, GermanyRegeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USAHuman Genetics Branch, National Institute of Mental Health, 35 Convent Drive, Bethesda, MD 20892, USAInstitute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, 24105 Kiel, GermanyBrazilian National Cancer Institute, Rua André Cavalcanti, 37, Rio de Janeiro 20231-050, RJ, BrazilBrazilian National Cancer Institute, Rua André Cavalcanti, 37, Rio de Janeiro 20231-050, RJ, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilLaboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, Curitiba 81531-990, PR, BrazilThe regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (<i>NR3C1</i>) 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 <i>NR3C1</i> in the genetically isolated Brazilian Mennonite population, we genotyped 20 <i>NR3C1</i> 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 <i>NR3C1</i> 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 <i>rs10482605*C</i> (OR = 4.74, <i>p</i>corr = 0.024) and the haplotype containing <i>TTCGTTGATT</i> (<i>rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T</i>, OR = 4.74, <i>p</i>corr = 0.048), as well as for the <i>CCT</i> haplotype (<i>rs41423247*C_ rs6877893*C_rs258763*T</i>), OR = 6.02, <i>p</i>corr = 0.030), but not to the differences in methylation or gene expression. Thus, <i>NR3C1</i> 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.https://www.mdpi.com/2073-4425/14/9/1805<i>NR3C1</i>HPAglucocorticoid receptorhaplotypeanabaptist populationmethylation |
| spellingShingle | Kathleen Liedtke Kolb Ana Luiza Sprotte Mira Eduardo Delabio Auer Isabela Dall’Oglio Bucco Carla Eduarda de Lima e Silva Priscila Ianzen dos Santos Valéria Bumiller-Bini Hoch Luana Caroline Oliveira Aline Borsato Hauser Jennifer Elisabeth Hundt Alan R. Shuldiner Fabiana Leão Lopes Teide-Jens Boysen Andre Franke Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima Gabriela Canalli Kretzschmar Angelica Beate Winter Boldt Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population Genes <i>NR3C1</i> HPA glucocorticoid receptor haplotype anabaptist population methylation |
| title | Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| title_full | Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| title_fullStr | Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| title_full_unstemmed | Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| title_short | Glucocorticoid Receptor Gene (<i>NR3C1</i>) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population |
| title_sort | glucocorticoid receptor gene i nr3c1 i polymorphisms and metabolic syndrome insights from the mennonite population |
| topic | <i>NR3C1</i> HPA glucocorticoid receptor haplotype anabaptist population methylation |
| url | https://www.mdpi.com/2073-4425/14/9/1805 |
| work_keys_str_mv | AT kathleenliedtkekolb glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT analuizasprottemira glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT eduardodelabioauer glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT isabeladallogliobucco glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT carlaeduardadelimaesilva glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT priscilaianzendossantos glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT valeriabumillerbinihoch glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT luanacarolineoliveira glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT alineborsatohauser glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT jenniferelisabethhundt glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT alanrshuldiner glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT fabianaleaolopes glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT teidejensboysen glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT andrefranke glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT luisfeliperibeiropinto glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT sheilacoelhosoareslima glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT gabrielacanallikretzschmar glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation AT angelicabeatewinterboldt glucocorticoidreceptorgeneinr3c1ipolymorphismsandmetabolicsyndromeinsightsfromthemennonitepopulation |