title: Identification and association of the single nucleotide polymorphisms, C-509T, C+466T and T+869C, of the TGF-β1 gene in patients with asthma and their influence on the mRNA expression level of TGF-β1.
abstract: Transforming growth factor-β1 (TGF-β1) is an important fibrogenic and immunomodulatory cytokine participating in the pathogenesis of a number of illnesses related to the growth, differentiation and migration of cells. It also plays a key role in inflammation, atherosclerosis, vascular inflammation and asthma. The aim of the present study was to evaluate the association between the expression of the TGF-β1 gene and its genetic polymorphisms, and the disease phenotype. The study comprised 173 patients with asthma, as well as 163 healthy volunteers as a control group. The gender profiles of the groups were similar (p=0.8415). Genotyping was performed by polymerase chain reaction (PCR)-high resolution melting (HRM). The results were verified by sequencing. Gene expression was evaluated by RT-PCR. This study evaluated the role and frequency of genetic polymorphisms (C-509T, C+466T and T+869C) of the TGF-β1 gene in the study group (patients with asthma) and the control group (healthy volunteers). The results obtained for the patients and healthy controls were as follows: C-509T single nucleotide polymorphism (SNP) (controls, TT/CT/CC-0.4444/0.5309/0.0247; patients, TT/CT/CC-0.3699/0.6012/0.0289), C+466T SNP (controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC-1.000/0.000/0.000) and T+869C SNP (controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC-1.000/0.000/0.000). Only the C-509T polymorphism was found to play a significant role in the pathogenesis of asthma, as well as a risk factor in the loss of the clinical control of the disease [TT vs. CC/CT, odds ratio (OR) 2.38; confidence interval (CI) 1.22-4.66; p=0.0103]. A significant difference was noted between the study and control groups with regard to the mRNA expression of TGF-β1 (p=0.0133). A higher level of expression of the TGF-β1 gene correlated with the time of diagnosis of patients over 16 years of age (p=0.0255). This study demonstrates that the C-509T SNP is a significant clinical risk factor for asthma and that the TGF-β1 cytokine contributes to the progression of the illness.
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90-153 Lodz, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Panek
authors.affiliation: Department of Pneumology and Allergology, Medical University of Lodz, 90-153 Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pietras
authors.affiliation: Students Research Group, Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90-153 Lodz, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Fabijan
authors.affiliation: Students Research Group, Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90-153 Lodz, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Zioło
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Wieteska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Małachowska
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 91-738 Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 90-153 Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
mesh_terms: D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1