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Glucocorticoid receptor haplotype and metabolic syndrome: the Lifelines cohort study. | LitMetric

AI Article Synopsis

  • - The study explores how certain genetic variations (SNPs) in the glucocorticoid receptor gene are linked to metabolic syndrome (MetS) in people with Cushing's syndrome, but past results have been mixed due to different populations and small sample sizes.
  • - Through a survey of over 12,000 adults, researchers identified five main haplotypes of the glucocorticoid receptor, but found that overall, these haplotypes didn't have a significant impact on MetS risk.
  • - However, haplotype 4, which includes a specific SNP (N363S), was associated with higher MetS risk in younger men and those with lower education levels, indicating that both genetics and environmental factors play a

Article 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.

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Source
http://dx.doi.org/10.1530/EJE-16-0534DOI Listing

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