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Introduction: Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. Objective: The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. Methods: A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. Results: We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p = 0.012, p = 0.009, p = 0.013, and p = 0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5′ to 3′; p = 0.0001). Polymorfism–Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p A, IVS1-89T>G, c.201delC, e IVS2-15G>A) no gene Ugrp2. Nossa análise genotípica mostrou que os genótipos Ugrp2 (IVS1-89T>G) TG e (c.201delC) CdelC e seus alelos menores foram associados a um aumento considerável no risco de HA em comparação com os controles (p = 0,012, p = 0,009, p = 0,013 e p = 0,037, respectivamente). Além disso, os haplótipos Ugrp2 (GTdelCG, GTdelCA) foram significativamente associados com hipertrofia de tonsila faríngea (quatro polimorfismos de nucleot’ ordenados de 5’ a 3’; p = 0,0001). A análise de interação polimorfismo-polimorfismo indicou uma forte interação entre genótipos combinados do gene Ugrp2 que contribuiu para hipertrofia de tonsila faríngea, bem como uma chance maior de seu diagnóstico (p |