title: Glucagon-like peptide-1 receptor gene polymorphism (Leu260Phe) is associated with morning cortisol in preschoolers.
abstract: Glucagon-like peptide-1 (GLP-1) has been shown to be a potent stress-regulating neuropeptide in animal models, but little is known about whether genetic polymorphisms that influence this peptide influence stress responses in humans. We therefore explored whether a missense mutation (rs1042044) in the GLP-1 receptor was associated with morning and evening salivary cortisol levels in preschool aged children. Morning and evening saliva samples and individual buccal swabs for DNA extraction were collected from seventy-seven preschool aged children. Salivary cortisol was assayed using a time-resolved fluorescence immunoassay with fluorometric end-point detection (DELFIA), and the rs1042044 single nucleotide polymorphism (SNP) was genotyped using allele specific TaqMan probes. Children homozygous for the phenylalanine (C) substitution in the GLP-1R gene had significantly higher morning salivary cortisol levels than children with other GLP-1R genotypes (p=0.029). Additionally, children with one or two copies of the phenylalanine (C) allele had significantly higher morning cortisol levels compared to children homozygous for the leucine (A) allele (p=0.008). Our results identify associations between a novel genetic variant of GLP-1R and hypothalamus-pituitary-adrenal (HPA) axis regulation. This polymorphism may have functional significance in stress-related psychiatric disorders.
authors.affiliation: Molecular Genetics Unit, Department of Biology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Haroon I
authors.initials: HI
authors.lastname: Sheikh
authors.forename: Lea R
authors.initials: LR
authors.lastname: Dougherty
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Hayden
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Klein
authors.forename: Shiva M
authors.initials: SM
authors.lastname: Singh
mesh_terms: D000483:Alleles; D000704:Analysis of Variance; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007118:Immunoassay; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D018027:Receptors, Glucagon / Q000235:genetics*; D012463:Saliva / Q000737:chemistry*; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D006854:Hydrocortisone