Vincent L Wester1,2, Jan W Koper1,2, Erica L T van den Akker3,2, Oscar H Franco4, Ronald P Stolk5, Elisabeth F C van Rossum6,2,7. 1. Department of Internal Medicine. 2. Obesity Center CGG. 3. Department of Pediatrics. 4. Department of EpidemiologyEramus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 5. Department of EpidemiologyUniversity Medical Center Groningen, Groningen, The Netherlands. 6. Department of Internal Medicine e.vanrossum@erasmusmc.nl. 7. Lifelines Cohort StudyGroningen, The Netherlands.
Abstract
OBJECTIVE: An excess of glucocorticoids (Cushing's syndrome) is associated with metabolic syndrome (MetS) features. Several single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence sensitivity to glucocorticoids and have been associated with aspects of MetS. However, results are inconsistent, perhaps due to the heterogeneity of the studied populations and limited samples. Furthermore, the possible association between functional GR SNPs and prevalence of MetS remains unexplored. DESIGN: Cross-sectional population-based cohort study. METHODS: MetS presence and carriage of functional GR SNPs (BclI, N363S, ER22/23EK, GR-9beta) were determined in 12 552 adult participants from Lifelines, a population-based cohort study in the Netherlands. GR SNPs were used to construct GR haplotypes. RESULTS: Five haplotypes accounted for 99.9% of all GR haplotypes found. No main effects of functional GR haplotypes on MetS were found, but the association of GR haplotype 4 (containing N363S) with MetS was influenced by interaction with age, sex and education status (P < 0.05). Stratified analysis revealed that haplotype 4 increased MetS presence in younger men (at or below the median age of 47; odds ratio 1.77, P = 0.005) and in people of low education status (odds ratio 1.48, P = 0.039). CONCLUSIONS: A glucocorticoid receptor haplotype that confers increased sensitivity to glucocorticoids appears to increase the risk of metabolic syndrome, but only among younger men and less educated individuals, suggesting gene-environment interactions.
OBJECTIVE: An excess of glucocorticoids (Cushing's syndrome) is associated with metabolic syndrome (MetS) features. Several single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence sensitivity to glucocorticoids and have been associated with aspects of MetS. However, results are inconsistent, perhaps due to the heterogeneity of the studied populations and limited samples. Furthermore, the possible association between functional GR SNPs and prevalence of MetS remains unexplored. DESIGN: Cross-sectional population-based cohort study. METHODS: MetS presence and carriage of functional GR SNPs (BclI, N363S, ER22/23EK, GR-9beta) were determined in 12 552 adult participants from Lifelines, a population-based cohort study in the Netherlands. GR SNPs were used to construct GR haplotypes. RESULTS: Five haplotypes accounted for 99.9% of all GR haplotypes found. No main effects of functional GR haplotypes on MetS were found, but the association of GR haplotype 4 (containing N363S) with MetS was influenced by interaction with age, sex and education status (P < 0.05). Stratified analysis revealed that haplotype 4 increased MetS presence in younger men (at or below the median age of 47; odds ratio 1.77, P = 0.005) and in people of low education status (odds ratio 1.48, P = 0.039). CONCLUSIONS: A glucocorticoid receptor haplotype that confers increased sensitivity to glucocorticoids appears to increase the risk of metabolic syndrome, but only among younger men and less educated individuals, suggesting gene-environment interactions.
Authors: Robin Lengton; Anand M Iyer; Eline S van der Valk; Ellen K Hoogeveen; Onno C Meijer; Bibian van der Voorn; Elisabeth F C van Rossum Journal: Obes Rev Date: 2021-11-27 Impact factor: 10.867
Authors: Pramod R Somvanshi; Synthia H Mellon; Janine D Flory; Duna Abu-Amara; Owen M Wolkowitz; Rachel Yehuda; Marti Jett; Leroy Hood; Charles Marmar; Francis J Doyle Journal: Am J Physiol Endocrinol Metab Date: 2019-07-19 Impact factor: 4.310