Association of Transforming Growth Factor-Beta 1 Promoter Variant -509 C/T with Bronchial Asthma in South Indian Populat
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Association of Transforming Growth Factor-Beta 1 Promoter Variant -509 C/T with Bronchial Asthma in South Indian Population Srinivas Bandaru,1,3,4 Vijaya Kumar Marri,2 Jyothy Akka,1 Mallika Alvala,3 and Hema Prasad Mundluru1
Abstract—Transforming growth factor-beta 1 (TGF-β1) is a multifunctional cytokine that plays a pivotal role in airway remodeling observed in the asthmatic airways. C to T base substitution at -509 promoter position in the TGF-β1 gene leads to its increased expression which contributes to airway remodeling in bronchial asthma. We sought to evaluate the association of TGF-β1 -509 C/T promoter variant with clinical asthma and varying degrees of disease severity. Three hundred and eighty-two clinically diagnosed asthma patients and 410 healthy controls were enrolled for the study. Patients were classified into severity classes according to the Global Initiative for Asthma (GINA) guidelines. TGF-β1 -509 C/T genotyping was carried out by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique. In the present study, we found significantly higher frequency of TT genotype in asthma patients compared to controls (for TT vs. CC, p = 0.020). In addition, a significant difference was observed in the frequency of C and T allele in patients and controls (for T vs. C, p=0.029). The heterozygous “CT” genotype was higher in moderate and severe asthmatics compared to mild subset of patients (for mild vs. moderate, p=0.037). However, there was no significant distribution and association of variant allele with the severity subsets. KEY WORDS: transforming growth factor-beta; -509 promoter polymorphism; bronchial asthma; asthma severity.
induce structural changes; in particular, transforming growth factor-beta 1 (TGF-β1) has shown to affect many structural cells in vitro and in vivo and has been wellimplicated in the remodeling process in asthma [1, 2]. Patients with asthma express increased TGF-β1 in the bronchoalveolar lavage (BAL) fluid in response to segmental allergen challenge, and TGF-β1 levels in the airway epithelium and submucosa correlate to airway basement membrane thickness, suggesting a direct role for TGF-β1 in airway remodeling [3]. In addition, bronchial biopsies of airway-smooth muscle tissue have shown higher mRNA expression for TGF-β1 from asthmatic patients as compared to non-asthmatic controls [4, 5]. These aforementioned findings clearly imply that TGF-β1 has a critical role to play in asthma pathogenesis. TGF-β1 is a seven-exon gene localized in chromosome 19q13.2 [6] which synthesizes 390 amino acid TGF-β1 prepropeptide. A particular C to T base substitution at position -509 from the first major transcription initiation site in the gene has been linked to promoter activity
INTRODUCTION Asthma is a chronic inflammatory disorder of the airways characterized by bronchial hyper-responsiveness that leads to airway remodeling and intractable airflow obstruction. Airways of individuals with asthma are characterized by a Th2-type inflammation, with an increased num
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