Association of <i>Ugrp2</i> gene polymorphisms with adenoid hypertrophy in the pediatric population

Atilla, Mahmut Huntürk; Özdaş, Sibel; Özdaş, Talih; Baştimur, Sibel; Muz, Sami Engin; Öz, Işılay; Kurt, Kenan; İzbirak, Afife; Babademez, Mehmet Ali; Vatandaş, Nilgün

doi:10.1016/j.bjorl.2017.07.004

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Brazilian Journal of Otorhinolaryngology

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Original articles • Braz. j. otorhinolaryngol. 84 (5) • Sep-Oct 2018 • https://doi.org/10.1016/j.bjorl.2017.07.004 copy

Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population^☆ ☆ Please cite this article as: Atilla MH, Özdaş S, Özdaş T, Baştimur S, Muz SE, Öz I, et al. Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population. Braz J Otorhinolaryngol. 2018;84:599-607.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

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 < 0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and with allergies (p = 0.003 and p = 0.0007, respectively).

Conclusion:

Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy. Therefore, we tried to underline the importance of genetic factors associated with adenoid hypertrophy and its related clinical phenotypes.

KEYWORDS
Adenoid hypertrophy; Asthma; Allergy; Ugrp2; Single nucleotide polymorphism

	Patients with AH (n = 114)	Healthy control children (n = 105)	p-Value
Age (years) (mean ± SD)	5.38 (1.532)	5.23 (1.712)	0.570^a a Mann-Whitney U test.
Gender, n (%)
Male	60 (53)	59 (56)	0.709^b b Fisher exact test.
Female	54 (47)	46 (44)	0.709^b b Fisher exact test.
Asthma (+), n (%)	30 (26)	14 (13)	0.042 ^b b Fisher exact test.
Allergy (+), n (%)	33 (29)	15 (14)	0.032 ^c c χ2 test.

SNPs	Genotype/allele	Controls (n = 105)	Cases (n = 114)	OR (95% CI)	p-Value
		n (%)	n (%)
IVS1-189G>A	G/G	101 (96)	109 (96)	1.00 (reference)	0.092^a a χ2 test.
	G/A	4 (4)	5 (4)	1.00 (0-0)
	A/A	0 (0)	0 (0)	-
	A^c c Assumed risk alleles.	0.02	0.02	1.00 (0-0)	1^b b Fisher exact test.
IVS1-89T>G	T/T	99 (94)	99 (87)	1.00 (reference)	0.012 ^a a χ2 test.
	T/G	6 (6)	15 (13)	2.50 (0.75-8.37)
	G/G	0 (0)	0 (0)	-
	G^c c Assumed risk alleles.	0.03	0.07	2.39 (0.79-7.81)	0.013 ^a a χ2 test.
201delC	C/C	105 (100)	106 (93)	1.00 (reference)	0.0097 ^a a χ2 test.
	C/delC	0 (0)	8 (7)	5 (1.25-20)
	delC/delC	0 (0)	0 (0)	-
	delC^c c Assumed risk alleles.	0.00	0.003	4.68 (1.0-9.2)	0.037 ^b b Fisher exact test.
IVS2-15G>A	G/G	105 (100)	113 (99)	1.00 (reference)	0.25^a a χ2 test.
	G/A	0 (0)	1 (1)	0.99 (0.07-10)
	A/A	0 (0)	0 (0)	-
	A^c c Assumed risk alleles.	0.00	0.01	0.99 (0.8-11.15)	1^a a χ2 test.

Nº	Haplotypes^a a The alleles of the haplotypes were arrayed as the location of in the SNPs UGRP2. Global haplotype association p-value = 0.049.				Frequencies		OR (95% CI)	p-Value
	IVS1-189G>A	IVS1-89T>G	c.201delC	IVS2-15G>A	Cases	Controls
1	G	T	C	G	0.8816	0.9500	1.00	-
2	G	G	C	G	0.0658	0.0286	2.72 (0.81-9.14)	0.011
3	A	T	C	G	0.0197	0.0214	1.09 (0.21-5.60)	0.92
4	G	T	DelC	G	0.0263	0	2528.32 (2523.00-2530.64)	<0.0001
5	G	T	DelC	A	0.0066	0	2523.96 (2523.88-2523.05)	<0.0001

Model	TBT	TBA	CVC
IVS1-89T>G	0.5394	0.5043	7/9
IVS1-89T>G_c.201delC	0.9877	0.4862	9/10
IVS1-189G>A_IVS1-89T>G_c.201delC	0.9877	0.4862	10/10

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[1] * Corresponding author. E-mail:s_unurlu@yahoo.com (S. Özdaş).