Related resources
Full-text held externally
Search for item elsewhere
University researcher(s)
Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype.
Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CEM, Donn RP
J Clin Endocrinol Metab. 2004;89:892-897.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
Abstract
Differences in glucocorticoid (GC) sensitivity may underlie both common diseases (e.g. hypertension) and variability in response to treatment with GCs (e.g. asthma). We tested the potential involvement of the GC receptor (GR) gene in mediating GC sensitivity using haplotype analysis and a low-dose dexamethasone suppression test. Linkage disequilibrium across the GR gene was determined in 216 U.K. Caucasians, and 116 had a 0.25-mg overnight dexamethasone suppression test. Very strong linkage disequilibrium was observed across the GR gene with only four haplotypes accounting for 95% of those observed. Haplotype pattern mining and linear regression analyses independently identified a three-marker haplotype, across intron B, to be significantly associated with low postdexamethasone cortisol (P = 0.03). Carriage of this haplotype occurred in 41% of the individuals with low postdexamethasone cortisol vs. 23% in the combined other quartiles (odds ratio 2.4, 95% confidence interval 0.9-6.3, P = 0.05). This is the first comprehensive, haplotype based analysis of the GR gene. A three-point haplotype, within intron B, is associated with enhanced sensitivity to GCs. This haplotype may help predetermine variation in clinical response to GC therapy and also assist the understanding of diseases related to GC production.
Keyword(s)
Adult; Alleles; Case-Control Studies; Chronic Disease; Dose-Response Relationship, Drug; Female; Gene Frequency; Genetic Markers; Genetic Screening; Haplotypes; Human; Linear Models; Linkage Disequilibrium; Male; Osmolar Concentration; Polymorphism, Single Nucleotide; Promoter Regions (Genetics); Support, Non-U.S. Gov't; administration & dosage: Dexamethasone; administration & dosage: Glucocorticoids; biosynthesis: Hydrocortisone; genetics: Drug Resistance; genetics: Introns; genetics: Psoriasis; genetics: Receptors, Glucocorticoid; metabolism: Lymphocytes