title: GLCCI1 and Glucocorticoid Receptor Genetic Diversity and Response to Glucocorticoid-Based Treatment of Graft-versus-Host Disease.
abstract: The genetic diversity of loci implicated in glucocorticoid (GC) response has been associated with interindividual variations in responsiveness to GC in various diseases, such as asthma and inflammatory bowel disorders. In acute graft-versus-host disease (aGVHD), similar differences of first-line therapy responsiveness are also observed, with approximately 40% of patients failing to respond to GC. Here, the distribution of functionally relevant single nucleotide polymorphisms (SNP) belonging to the GC-induced transcript 1 GLCCI1 (rs37972) and the glucocorticoid receptor (rs41423247, rs6195 and rs6198) gene loci were analyzed alongside clinical factors for their association with the response to corticosteroids in aGVHD. The frequencies of variant alleles did not differ significantly between corticoresistant patients, their donors, and their corticosensitive peers (P = .10 to 1.00). Severe and early onset of aGVHD, bone marrow as the stem cell source, and an HLA mismatch were associated with the failure to respond to GC in logistic regression. After including the single SNPs to the model, carriers of the rs41423247 polymorphism had a higher probability of responding to GC, whereas all other polymorphisms did not affect the likelihood of response.
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.
authors.forename: Alix
authors.initials: A
authors.lastname: O'Meara
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMRS-1160, F-75010 Paris, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.
authors.forename: Aliénor
authors.initials: A
authors.lastname: Xhaard
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fortier
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Marzais
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Sicre de Fontbrune
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: Hematology Transplantation, Assistance Publique-Hôpitaux de Paris, Saint Louis Hospital, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS-1160, F-75010 Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMRS-1160, F-75010 Paris, France; Laboratoire Jean Dausset and LabEx Transplantex, Hôpital Saint Louis, Paris, France. Electronic address: tamouza.ryad@gmail.com.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005938:Glucocorticoids / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000276:immunology; D012306:Risk; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: C561807:GLCCI1 protein, human; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D011965:Receptors, Glucocorticoid
keywords: Glucocorticoid resistance; Graft-versus-host disease; Hematopoietic; Stem cell; Transplantation