title: Admixture of beneficial and unfavourable variants of GLCCI1 and FCER2 in Roma samples can implicate different clinical response to corticosteroids.
abstract: Variants of glucocorticoid induced transcript 1 (GLCCI1) result decreased response to inhaled corticosteroids, while intronic variant of low-affinity IgE receptor (FCER2) is associated with exacerbation rates in children with asthma. We examined the ethnic differences, allele and genotype frequencies of two linked single nucleotide polymorphisms (rs37972, rs37973) of GLCCI1 and rs28364072 intronic variant of FCER2 gene in average Roma and Hungarian population. A study population of 474 healthy Roma and 397 Hungarian subjects were characterized for GLCCI1 and FCER2 polymorphisms using real time polymerase chain reaction (PCR) assay and PCR-restriction fragment length polymorphism method. The rs37972 and rs37973 polymorphisms in GLCCI1 were found in 100% linkage disequilibrium both in Romas and in Hungarians. We found significant differences between the two groups regarding both minor allele frequencies (54.5 vs. 43.8%, p ≤ 0.01) and homozygous genotype (31.6 vs. 21.3%, p ≤ 0.01) of GLCCI1. For FCER2 rs28364072 the homozygous variant genotype was present in 2.8% in Romas, while in Hungarians it was 5.8% (p = 0.032). The opposite changes of these two polymorphisms strongly suggest that contrary current belief analyses of GLCCI1 variants are insufficient for personalised glucocorticoid therapies in different populations.
authors.affiliation: Department of Medical Genetics, University of Pecs, Szigeti 12, Pecs, 7624, Hungary.
authors.forename: Renata
authors.initials: R
authors.lastname: Szalai
authors.forename: Petra
authors.initials: P
authors.lastname: Matyas
authors.forename: Dalma
authors.initials: D
authors.lastname: Varszegi
authors.forename: Marton
authors.initials: M
authors.lastname: Melegh
authors.forename: Lili
authors.initials: L
authors.lastname: Magyari
authors.forename: Luca
authors.initials: L
authors.lastname: Jaromi
authors.forename: Katalin
authors.initials: K
authors.lastname: Sumegi
authors.forename: Balazs
authors.initials: B
authors.lastname: Duga
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Kovesdi
authors.forename: Kinga
authors.initials: K
authors.lastname: Hadzsiev
authors.forename: Bela
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006814:Hungary; D037181:Lectins, C-Type / Q000235:genetics*; D015810:Linkage Disequilibrium; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D017455:Receptors, IgE / Q000235:genetics*; D006178:Romani People / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones; C546930:FCER2 protein, human; C561807:GLCCI1 protein, human; D037181:Lectins, C-Type; D011965:Receptors, Glucocorticoid; D017455:Receptors, IgE
references.citation: J Biol Chem. 2011 Sep 23;286(38):32883-9
references.pmid: 21799018
references.citation: J Allergy Clin Immunol. 2010 Feb;125(2):295-302; quiz 303-4
references.pmid: 20159237
references.citation: Eur J Public Health. 2010 Oct;20(5):549-54
references.pmid: 20650945
references.citation: Br Med Bull. 2000;56(4):1054-70
references.pmid: 11359637
references.citation: Am J Hum Genet. 2004 Oct;75(4):596-609
references.pmid: 15322984
references.citation: Pharmacogenomics. 2012 Feb;13(3):243-5
references.pmid: 22304573
references.citation: Pharmacogenomics J. 2011 Dec;11(6):383-92
references.pmid: 21987090
references.citation: Ethn Health. 2003 Aug;8(3):223-49
references.pmid: 14577997
references.citation: Am J Hum Genet. 2001 Dec;69(6):1314-31
references.pmid: 11704928
references.citation: J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S73-80
references.pmid: 20176269
references.citation: BMC Med Genet. 2001;2:5
references.pmid: 11299048
references.citation: Neuromolecular Med. 2010 Jun;12(2):164-78
references.pmid: 19844812
references.citation: J Allergy Clin Immunol. 2007 Dec;120(6):1285-91
references.pmid: 17980418
references.citation: Curr Opin Pharmacol. 2010 Jun;10(3):226-35
references.pmid: 20646961
references.citation: J Exp Med. 1988 Apr 1;167(4):1406-16
references.pmid: 2965737
references.citation: Pediatr Nephrol. 2012 Sep;27(9):1595-9
references.pmid: 22660954
references.citation: Clin Exp Immunol. 2010 Oct;162(1):12-23
references.pmid: 20831712
references.citation: N Engl J Med. 2011 Sep 29;365(13):1173-83
references.pmid: 21991891
references.citation: J Infect Dis. 2011 Jul;204 Suppl 1:S353-65
references.pmid: 21666185
references.citation: Trans Am Clin Climatol Assoc. 2011;122:27-33
references.pmid: 21686206