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The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis

DOI: 10.1186/1471-2466-12-41

Keywords: Genotype, Phenotype, Variability, Genetic modulation, Angiotensin-converting Enzyme

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A cross-sectional study was performed, from 2009 to 2011, at University of Campinas – UNICAMP. We analyzed 180 patients for the most frequent mutations in the CFTR gene, presence of the ACE gene D/I polymorphism and clinical characteristics of CF.There was an association of the D/D genotype with early initiation of clinical manifestations (OR: 1.519, CI: 1.074 to 2.146), bacterium Burkholderia cepacia colonization (OR: 3.309, CI: 1.476 to 6.256) and Bhalla score (BS) (p?=?0.015). The association was observed in subgroups of patients which were defined by their CFTR mutation genotype (all patients; subgroup I: no mutation detected; subgroup II: one CFTR allele identified to mutation class I, II or III; subgroup III: both CFTR alleles identified to mutation class I, II and/or III).An association between the D allele in the ACE gene and the severity of CF was found in our study.CFTR gene mutations are crucial in modulating the severity of cystic fibrosis (CF), along with environmental factors and modifier genes [1-7]. CF occurs with heterogeneous clinical presentation. Among the clinical symptoms, that of highest variability is lung disease [5], and modifier genes have been analyzed and associated as possible factors that influence this clinical response [3,7].The ACE gene codifies the Angiotensin Converting Enzyme (ACE). Based on the pro-inflammatory property of the ACE protein [8,9], the ACE gene was selected as a possible genetic marker for clinical denotation in CF. The ACE enzyme catalyzes the conversion of angiotensin I to angiotensin II peptide, acting in the blood pressure control and the electrolyte balance of blood, being an important vasoconstrictor and stimulant of aldosterone [8,10].The ACE gene is located on region 17q23.3 [11]. A biallelic polymorphism, named as I (insertion) and D (deletion), with D allele characterized by a deletion of the 287 pb DNA fragment in intron 16, affects the level of the ACE enzyme. The polymorphism determines the amount of A


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