title: A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-β1 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation.
abstract: The aim of the present study was to identify polymorphic forms of the nuclear receptor subfamily 3, group C, member 1 (NR3C1) and transforming growth factor β1 (TGF-β1) genes and evaluate their impact on the expression levels of interleukin (IL)-5 and IL‑15 in asthma. The study was conducted on a control group consisting of 91 people (54 women and 37 men). The patient group consisted of 130 participants (86 women and 44 men). Genotyping was performed by polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP) and PCR‑high resolution melting (HRM) methods. Interleukin expression was measured by reverse transcription‑quantitative polymerase chain reaction. The frequency of the polymorphic forms in the analyzed group were observed to be: Tth111I (rs10052957) controls AA 0.0440, AG 0.5714, GG 0.3846, patients AA 0.1538/AG 0.4692, GG 0.3769; ER22/23EK (rs6189 /rs6190) controls AG 0.0556, GG 0.9444, patients AG 0.0385, GG 0.9615; N363S (rs6195) controls AA 0.6444, AG 0.2667, GG 0.0889, patients AA 0.7846, AG 0.1385, GG 0.0769; BclI (rs41423247) controls CC 0.0879, CG 0.5604, GG 0.3516, patients CC 0.1008, CG 0.5736, GG 0.3256; C‑509T (rs1800469) controls TT 0.0805, CT 0.6322, CC 0.2874, patients TT 0.1102, CT 0.5669, CC 0.3228. The results indicated that the C‑509T single nucleotide polymorphism (SNP) of the TGF-β1 gene contributed to an increase in the IL‑5 mRNA expression levels. The GG genotype of the N363S SNP of the NR3C1 gene was observed to result in an increase in the expression levels of IL‑15. The present study indicated that the selected SNPs of the NR3C1 and TGF‑β1 genes demonstrate a regulatory effect on the expression of IL‑5 and IL‑15. Therefore, genetic variation affects inflammation in asthma and the clinical course of the disease.
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz 90‑153, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Panek
authors.affiliation: Students Research Group, The Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz 90‑153, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Jonakowski
authors.affiliation: Students Research Group, The Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz 90‑153, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Zioło
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz 92‑215, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Wieteska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology of Medical University of Lodz, Lodz 91‑738, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Małachowska
authors.affiliation: Department of Pneumology and Allergology, Medical University of Lodz, Lodz 90‑153, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pietras
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz 92‑215, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz 90‑153, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics*; D015848:Interleukin-5 / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D019409:Interleukin-15; D015848:Interleukin-5; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D053773:Transforming Growth Factor beta1