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1
المؤلفون: Kamble, Prasad G., Gustafsson, Stefan, Pereira, Maria J., Lundkvist, Per, Cook, Naomi, Lind, Lars, Franks, Paul W., Fall, Tove, Eriksson, Jan W., Ingelsson, Erik
المصدر: Upsala Journal of Medical Sciences EXODIAB: Excellence of Diabetes Research in Sweden EpiHealth: Epidemiology for Health. 122(4):234-242
مصطلحات موضوعية: Genotype-based recall, metabolism, PPARG Pro12Ala, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics
الوصف: Aim: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype–phenotype relationships. Methods: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. Results: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. Conclusions: Our report highlights that from a practical perspective, GBR can be used to study genotype–phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
الوصول الحر: https://lup.lub.lu.se/record/295bc90f-0dbe-453d-a392-03042308032bTest
http://dx.doi.org/10.1080/03009734.2017.1405127Test -
2دورية أكاديمية
المؤلفون: Prasad G. Kamble, Stefan Gustafsson, Maria J. Pereira, Per Lundkvist, Naomi Cook, Lars Lind, Paul W. Franks, Tove Fall, Jan W. Eriksson, Erik Ingelsson
المصدر: Upsala Journal of Medical Sciences, Vol 122, Iss 4, Pp 234-242 (2017)
مصطلحات موضوعية: Genotype-based recall, metabolism, PPARG Pro12Ala, Medicine
الوصف: Aim: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype–phenotype relationships. Methods: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. Results: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. Conclusions: Our report highlights that from a practical perspective, GBR can be used to study genotype–phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
وصف الملف: electronic resource
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المؤلفون: Kamble, Prasad G.
المساهمون: Eriksson, Jan W, Dahlman, Ingrid, Professor
المصدر: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine.
مصطلحات موضوعية: human adipose tissue, nuclear receptors, glucocorticoids, estrogen, PPARγ, lipocalin 2, glucose uptake, lipolysis, adipogenesis, genotype-based recall
الوصف: Nuclear receptors modulate expression of genes involved in adipose tissue (AT) metabolism. Their improved understanding may provide new treatment options for metabolic disorders such as obesity, insulin resistance (IR) and type 2 diabetes (T2D).This thesis explored the role of nuclear receptors, mainly, glucocorticoid and estrogen receptors (GR and ER, respectively) and peroxisome proliferator-activated receptor gamma (PPARγ), and their interplay in the regulation of metabolic function and dysfunction in human AT.In Paper I, the regulation of adipokine lipocalin 2 (LCN2) expression by synthetic glucocorticoid, dexamethasone and effect of LCN2 on glucose and lipid metabolism in AT were studied. In pre-menopausal but not post-menopausal women or men, dexamethasone upregulated LCN2 gene expression, which also correlated with markers of obesity and IR. LCN2 inhibited adipocyte glucose uptake.In Paper II, the effect of estrogen (E2) and its interaction with GR in LCN2 regulation in AT from post-menopausal women were examined. E2 increased LCN2 expression, what seems to be mediated by ERβ. E2 and dexamethasone co-treatment increased LCN2 gene expression in presence of ERα but not ERβ antagonist. Dexamethasone decreased ERα, while increased ERβ gene expression.In Paper III and IV, the feasibility of genotype-based recall (GBR), a participant recruitment approach, was tested by undertaking clinical and AT phenotyping of different PPARγ Pro12Ala carriers. The baseline characteristics were comparable between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro group also accompanied with a higher antilipolytic effect of insulin after oral glucose. Adipocyte glucose uptake and adipogenesis remained unchanged between genotypes.Overall, LCN2 can induce IR in human AT and may mediate metabolic defects by excess glucocorticoids in pre-menopausal women. GR selectively interacts with ERα and ERβ, the latter two acts oppositely to control LCN2 expression in AT. PPARγ Pro12Ala had no major effect on clinical and adipose phenotype, likely due to a small sample size in relation to the modest effect the Ala variant or tissues other than adipose could be critical in conferring protection by Pro12Ala against T2D risk. Further, the GBR approach deemed feasible, however, would be more suitable in the characterization of rare genetic variants.
وصف الملف: electronic
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المؤلفون: Per Lundkvist, Maria J. Pereira, Lars Lind, Paul W. Franks, Jan W. Eriksson, Prasad G. Kamble, Tove Fall, Erik Ingelsson, Stefan Gustafsson, Naomi L. Cook
المصدر: Upsala Journal of Medical Sciences, Vol 122, Iss 4, Pp 234-242 (2017)
Upsala Journal of Medical Sciencesمصطلحات موضوعية: Male, 0301 basic medicine, Heterozygote, medicine.medical_specialty, Genotype, lcsh:Medicine, Pilot Projects, Type 2 diabetes, Endocrinology and Diabetes, PPARG Pro12Ala, 03 medical and health sciences, Genetic variation, medicine, Humans, Missense mutation, Aged, Medicinsk genetik, Genetics, business.industry, lcsh:R, Original Articles, General Medicine, Middle Aged, Anthropometry, medicine.disease, PPAR gamma, Minor allele frequency, Phenotype, 030104 developmental biology, Endokrinologi och diabetes, Cohort, Genotype-based recall, Medical genetics, Female, business, metabolism, Medical Genetics, Genome-Wide Association Study
الوصف: Aim: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype–phenotype relationships. Methods: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. Results: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. Conclusions: Our report highlights that from a practical perspective, GBR can be used to study genotype–phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91a97921f3614ce8bb7bb2479ee191a9Test
https://doi.org/10.1080/03009734.2017.1405127Test -
5دورية أكاديمية
المؤلفون: Franks, Paul W., Paré, Guillaume
المصدر: Current Diabetes Reports; 16(7), no 57 (2016) ; ISSN: 1534-4827
مصطلحات موضوعية: Medical Genetics, Cardiometabolic, Gene-lifestyle interaction, Genomic, Genotype-based recall, Obesity, Recall by genotype, Systems biology, Variance heterogeneity
الوصف: The genome is often the conduit through which environmental exposures convey their effects on health and disease. Whilst not all diseases act by directly perturbing the genome, the phenotypic responses are often genetically determined. Hence, whilst diseases are often defined has having differing degrees of genetic determination, genetic and environmental factors are, with few exceptions, inseparable features of most diseases, not least type 2 diabetes. It follows that to optimize diabetes, prevention and treatment will require that the etiological roles of genetic and environmental risk factors be jointly considered. As we discuss here, studies focused on quantifying gene-environment and gene-treatment interactions are gathering momentum and may eventually yield data that helps guide health-related choices and medical interventions for type 2 diabetes and other complex diseases.
العلاقة: https://lup.lub.lu.se/record/d15b3e16-ca47-4cfd-9634-37786e2530bfTest; http://dx.doi.org/10.1007/s11892-016-0758-yTest; scopus:84966312197; pmid:27155607; wos:000377938700002
الإتاحة: https://doi.org/10.1007/s11892-016-0758-yTest
https://lup.lub.lu.se/record/d15b3e16-ca47-4cfd-9634-37786e2530bfTest -
6مورد إلكتروني
مستخلص: Nuclear receptors modulate expression of genes involved in adipose tissue (AT) metabolism. Their improved understanding may provide new treatment options for metabolic disorders such as obesity, insulin resistance (IR) and type 2 diabetes (T2D). This thesis explored the role of nuclear receptors, mainly, glucocorticoid and estrogen receptors (GR and ER, respectively) and peroxisome proliferator-activated receptor gamma (PPARγ), and their interplay in the regulation of metabolic function and dysfunction in human AT. In Paper I, the regulation of adipokine lipocalin 2 (LCN2) expression by synthetic glucocorticoid, dexamethasone and effect of LCN2 on glucose and lipid metabolism in AT were studied. In pre-menopausal but not post-menopausal women or men, dexamethasone upregulated LCN2 gene expression, which also correlated with markers of obesity and IR. LCN2 inhibited adipocyte glucose uptake. In Paper II, the effect of estrogen (E2) and its interaction with GR in LCN2 regulation in AT from post-menopausal women were examined. E2 increased LCN2 expression, what seems to be mediated by ERβ. E2 and dexamethasone co-treatment increased LCN2 gene expression in presence of ERα but not ERβ antagonist. Dexamethasone decreased ERα, while increased ERβ gene expression. In Paper III and IV, the feasibility of genotype-based recall (GBR), a participant recruitment approach, was tested by undertaking clinical and AT phenotyping of different PPARγ Pro12Ala carriers. The baseline characteristics were comparable between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro group also accompanied with a higher antilipolytic effect of insulin after oral glucose. Adipocyte glucose uptake and adipogenesis remained unchanged between genotypes. Overall, LCN2 can induce IR in human AT and may mediate metabolic defects by excess glucocorticoids in pre-menopausal women. GR selectively interacts with ERα and ERβ, the latter two acts oppositely to contr
مصطلحات الفهرس: human adipose tissue, nuclear receptors, glucocorticoids, estrogen, PPARγ, lipocalin 2, glucose uptake, lipolysis, adipogenesis, genotype-based recall, Medical and Health Sciences, Medicin och hälsovetenskap, Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text
URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-357119Test
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 1489 -
7مورد إلكتروني
مستخلص: Nuclear receptors modulate expression of genes involved in adipose tissue (AT) metabolism. Their improved understanding may provide new treatment options for metabolic disorders such as obesity, insulin resistance (IR) and type 2 diabetes (T2D). This thesis explored the role of nuclear receptors, mainly, glucocorticoid and estrogen receptors (GR and ER, respectively) and peroxisome proliferator-activated receptor gamma (PPARγ), and their interplay in the regulation of metabolic function and dysfunction in human AT. In Paper I, the regulation of adipokine lipocalin 2 (LCN2) expression by synthetic glucocorticoid, dexamethasone and effect of LCN2 on glucose and lipid metabolism in AT were studied. In pre-menopausal but not post-menopausal women or men, dexamethasone upregulated LCN2 gene expression, which also correlated with markers of obesity and IR. LCN2 inhibited adipocyte glucose uptake. In Paper II, the effect of estrogen (E2) and its interaction with GR in LCN2 regulation in AT from post-menopausal women were examined. E2 increased LCN2 expression, what seems to be mediated by ERβ. E2 and dexamethasone co-treatment increased LCN2 gene expression in presence of ERα but not ERβ antagonist. Dexamethasone decreased ERα, while increased ERβ gene expression. In Paper III and IV, the feasibility of genotype-based recall (GBR), a participant recruitment approach, was tested by undertaking clinical and AT phenotyping of different PPARγ Pro12Ala carriers. The baseline characteristics were comparable between genotypes. Compared to fasting, a decreased hormone-sensitive lipase gene expression in Pro/Pro group also accompanied with a higher antilipolytic effect of insulin after oral glucose. Adipocyte glucose uptake and adipogenesis remained unchanged between genotypes. Overall, LCN2 can induce IR in human AT and may mediate metabolic defects by excess glucocorticoids in pre-menopausal women. GR selectively interacts with ERα and ERβ, the latter two acts oppositely to contr
مصطلحات الفهرس: human adipose tissue, nuclear receptors, glucocorticoids, estrogen, PPARγ, lipocalin 2, glucose uptake, lipolysis, adipogenesis, genotype-based recall, Medical and Health Sciences, Medicin och hälsovetenskap, Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text
URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-357119Test
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 1489 -
8مورد إلكتروني
مستخلص: AIM: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships. METHODS: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. RESULTS: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. CONCLUSIONS: Our report highlights that from a practical perspective, GBR can be used to study genotype-phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
مصطلحات الفهرس: Genotype-based recall, PPARG Pro12Ala, metabolism, Endocrinology and Diabetes, Endokrinologi och diabetes, Medical Genetics, Medicinsk genetik, Article in journal, info:eu-repo/semantics/article, text
URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-342240Test
Upsala Journal of Medical Sciences, 0300-9734, 2017, 122:4, s. 234-242 -
9مورد إلكتروني
مستخلص: AIM: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships. METHODS: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. RESULTS: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. CONCLUSIONS: Our report highlights that from a practical perspective, GBR can be used to study genotype-phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
مصطلحات الفهرس: Genotype-based recall, PPARG Pro12Ala, metabolism, Endocrinology and Diabetes, Endokrinologi och diabetes, Medical Genetics, Medicinsk genetik, Article in journal, info:eu-repo/semantics/article, text
URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-342240Test
Upsala Journal of Medical Sciences, 0300-9734, 2017, 122:4, s. 234-242 -
10مورد إلكتروني
مستخلص: AIM: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships. METHODS: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.14. It has also been shown to affect ligand binding and transcription, and carriage of the minor allele (Ala12) is associated with a reduced risk of type 2 diabetes. We re-invited 39 Pro12Pro, 34 Pro12Ala, and 30 Ala12Ala carriers and performed detailed anthropometric and serological assessments. RESULTS: The participation rates in the GBR study were 31%, 44%, and 40%, and accordingly we included 12, 15, and 13 individuals with Pro12Pro, Pro12Ala, and Ala12Ala variants, respectively. There were no differences in anthropometric or metabolic variables among the different genotype groups. CONCLUSIONS: Our report highlights that from a practical perspective, GBR can be used to study genotype-phenotype relationships. This approach can prove to be a valuable tool for follow-up findings from large-scale genetic discovery studies by undertaking detailed phenotyping procedures that might not be feasible in large studies. However, our study also illustrates the need for a larger pool of genotyped or sequenced individuals to allow for selection of rare variants with larger effects that can be examined in a GBR study of the present size.
مصطلحات الفهرس: Genotype-based recall, PPARG Pro12Ala, metabolism, Endocrinology and Diabetes, Endokrinologi och diabetes, Medical Genetics, Medicinsk genetik, Article in journal, info:eu-repo/semantics/article, text
URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-342240Test
Upsala Journal of Medical Sciences, 0300-9734, 2017, 122:4, s. 234-242
النص الكامل 