title: Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease.
abstract: Cortisol is involved in many physiological processes, including immunosuppressive and anti-inflammatory actions, and therefore cortisol and its synthetic analogs are widely used to treat a large number of diseases. In glucocorticoid treatment, a large variability of clinical responses is observed. This variability may, in part, be ascribed to genetic variation in the glucocorticoid receptor (GR) gene. In this review we present a catalogue of the various single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor gene and their consequences for human health and disease. Many different GR SNP association studies have been described. However, most studies come down to only a few SNPs reported with different annotations. In this review we clarified these different annotations to uniform names. Most associations between GR SNPs and phenotype have been found in body composition, metabolism, the cardiovascular system, the immune system and psychiatric illnesses. However, many associations have not been replicated (yet), and future replication studies and meta-analyses are needed. There is a substantial body of evidence for GR SNPs to have effects on clinical phenotype. However, as most SNP frequencies are low and their variation is within the range of the general population, the impact of a single SNP for health and disease in the general population is probably modest. However, in-depth studying of the molecular mechanisms of repeatedly observed clinical associations could lead to new possibilities for drug development. In particular the development of selective glucocorticoid receptor modulators holds promise.
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Erasmus MC, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Erasmus MC, The Netherlands.
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.affiliation: Department of Pediatrics, Section Endocrinology, Erasmus MC-Sophia, Rotterdam, The Netherlands. Electronic address: e.l.t.vandenakker@erasmusmc.nl.
authors.forename: Erica L T
authors.initials: EL
authors.lastname: van den Akker
mesh_terms: D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: D011965:Receptors, Glucocorticoid
keywords: Glucocorticoid receptor gene polymorphism haplotype cortisol