Vitamin D levels in children with recurrent tonsillitis

doi:10.1016/j.ijporl.2010.12.006

International Journal of Pediatric Otorhinolaryngology

Volume 75, Issue 3, March 2011, Pages 364-367

https://doi.org/10.1016/j.ijporl.2010.12.006 Get rights and content

Abstract

Aim

Although recurrent tonsillitis can be the consequence of defects in immune system, the exact etiology of recurrent tonsillitis is not clear. In this study, our aim was to determine the serum vitamin D levels and vitamin D receptor polymorphism among children undergone tonsillectomy due to the recurrent tonsillitis.

Methods

A 106 children undergone tonsillectomy due to recurrent tonsillitis and a 127 healthy children aging between 2 and 12 years were enrolled in this study, to determine serum 25-hydroxyvitamin D level and vitamin D receptor gene polymorphisms (Apa1, Taq 1, fok1). Serum vitamin D level was measured with ELISA (nmol/L) and receptor gene polymorphism was determined by PCR. Vitamin D serum level below 80 nmol/L was accepted as insufficient.

Results

The average serum vitamin D level was 176 ± 79 nmol/L in recurrent tonsillitis group and 193 ± 56 nmol/L in control group. There was no significant difference between the groups (p = 0.13). In recurrent tonsillitis group, 18% (n = 15) of children had their serum vitamin D levels below 80 nmol/L. The vitamin D receptor gene polymorphism (APA1, TAQ 1, FOK 1) in each group was compared (AA, Aa, aa, TT, Tt, tt, FF, Ff, ff). There was no significant difference between the two groups. The vitamin D serum levels and receptor sub-genotypes are also compared, and there was no significant difference between the groups.

Conclusion

There is no difference between the serum vitamin D level and receptor gene polymorphism among children with recurrent tonsillitis and healthy children. But vitamin D insufficiency is more prevalent in children with recurrent tonsillitis group (18%).

Introduction

Pathogenesis of recurrent tonsillitis in children is unclear [1]. Why do children have tonsillitis or infectious diseases in winter more frequently? This question can be answered, based on the life style of children during the winter and the epidemiologic data. Is the diminished sun-light in winter as of importance? The role of sun-light in vitamin D synthesis is well-known. Is the immune system negatively affected by the diminished sun-light and reduced vitamin D synthesis during winter? Do the diminished sun-light and reduced vitamin D synthesis during winter negatively affect the immune system and facilitate infections during winter? These are important questions needed to be answered.

Palatine tonsils play a crucial role in recognizing the airborne antigens through the macrophages located in the crypts [2]. Antigens are engulfed by the Toll-like receptor (TLR) located on the macrophages after they are taken up by the crypt epithelial cells [3]. Function of the TLR is to recognize the structural molecules of the pathogens that are different from the eukaryotes [3]. Expression of the TLR's shows variability during recurrent tonsillitis [4]. Also, activation of TLR has been shown to cause increased expression of vitamin D receptor gene and vitamin D hydroxylase which is necessary for the synthesis of vitamin D [5].

After the recognition of the pathogen, 1,25-dihydroxyvitamin D is synthesized inside the macrophage using the extracellular 25-hydroxyvitamin D taken by endocytosis [6]. Vitamin D receptor (VDR) is encoded by the VDR gene located on 12q13.1 gene locus [7]. VDR gene shows polymorphism and the most known three polymorphisms are Apa1, Fok1, taq1 [7], [8], [9]. Endogenously synthesized 1,25-dihydroxyvitamin D binds to VDR to stimulate the endogen defensin genes that increase cathelicidin synthesis, which has direct antimicrobial activity to the bacteria and viruses [5], [10], [11], [12], [13]. Active form of vitamin D plays major regulatory role in immune system while vitamin D₃ augments the macrophage functions like chemotaxis, phagocytosis and bactericidal effect [14].

In this study, our aim is to compare the serum vitamin D levels in children with recurrent tonsillitis and healthy children. We also look for the possible relationship between the recurrent tonsillitis and the most common VDR gene polymorphisms.

Section snippets

Study design

This clinical prospective case–control, involving fall, winter and spring seasons (9-month period), was carried out among children that were between 2 and 12 years of age performed in the Departments of Pediatrics and Otolaryngology at Istanbul University, Istanbul School of Medicine. Ethical committee approval was taken before the study was performed recurrent tonsillitis (Fig. 1).

The eligibility criteria for participants

Inclusion criteria for the recurrent tonsillitis group (Group-1) are as follows; (1) more than 6 episodes of acute

Results

During the 9-month course of the trial, blood samples were obtained from 233 children that met the participation criteria. A 106 patient were assigned to Group-1 (recurrent tonsillitis) and 127 healthy children were assigned to Group-2. Four patients in Group-1, 21 patients in Group-2 were excluded from the trial due to hemolyzed blood samples. Measurement of serum 25-hydroxyvitamin D levels and isolation of DNA were performed for the 102 patients in Group-1 and 106 patients in Group-2. In

Discussion

Serum vitamin D level and genetic polymorphism of VDRs located on macrophages cause alterations in immune cell functions [8], [19]. In this study, we look into the relationship between serum vitamin D level and vitamin D receptor polymorphism of children with recurrent tonsillitis. This trial is one of the leading trials studying the relationship between vitamin D serum level and recurrent tonsillitis in order to clarify the etiology of recurrent tonsillitis.

In this study serum

Acknowledgement

We would like to thank Ayça Erkin for rendering this paper to English grammar.

References (20)

M.J. Lange et al.
Toll-like receptors in tonsillar epithelial cells
Int. J. Pediatr. Otorhinolaryngol.
(2009)
A.G. Uitterlinden et al.
Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states
J. Steroid Biochem. Mol. Biol.
(2004)
A.G. Uitterlinden et al.
Genetics and biology of vitamin D receptor polymorphisms
Gene
(2004)
J.H. White
Vitamin D as a inducer of cathelicidin antimicrobial peptide expression: past, present and future
J. Steroid Biochem. Mol. Biol.
(2010)
G. McGillivary et al.
A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media
Mol. Immunol.
(2007)
M.F. Holick
Vitamin D status: measurement interpretation, and clinical application
Ann. Epidemiol.
(2009)
B.W. Hollis
Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D
J. Nutr.
(2005)
M.F. Holick
Calcium and vitamin D. Diagnostics and therapeutics
Clin. Lab. Med.
(2000)
M. Hewison
Vitamin D and the immune system: new perspectives on an old theme
Endocrinol. Metab. Clin. N. Am.
(2010)
R.J. Gaffney et al.
Bacteriology of normal and diseased tonsils assessed by fine-needle aspiration: haemophilus influenzae and the pathogenesis of recurrent acute tonsillitis
Clin. Otolaryngol. Allied Sci.
(1998)

There are more references available in the full text version of this article.

Cited by (23)

1,25(OH)<inf>2</inf>D<inf>3</inf> and specific IgE levels in children with recurrent tonsillitis, and allergic rhinitis
2013, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
Yildiz et al. [19], they reported that serum 1,25(OH)2D3 levels were lower in the RT group than in healthy children similar to our study. Whereas, Aydın et al. [20] found no difference in serum 1,25(OH)2D3 level or VDR gene polymorphism between children with RT and healthy children. VDD was more prevalent in children with RT (18%).
We investigated 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] and specific immunoglobulin E (IgE) levels in children with recurrent tonsillitis (RT) plus allergic rhinitis (AR).
Thirty children with RT + AR were included in the study group, and 30 healthy children comprised the control group. AR-related symptoms were determined using a symptom scale. 1,25(OH)₂D₃ and specific IgE measurements were made in both groups.
The 1,25(OH)₂D₃ value was significantly lower in the RT + AR group than in the control group. Specific IgE (mixed) panels were in normal limits in both groups; whereas specific IgE (mixed) grass pollen panel value of RT + AT group was significantly higher than that of the control group. Higher nasal itching, nasal obstruction, and concha edema scores were related to significantly higher specific IgE values for the (mixed) grass pollen panel, whereas higher sneeze scores were related to higher specific IgE values for the (mixed) pediatric panel.
Children with grass pollen allergy may not be exposed to sufficient sunlight. With reduced 1,25(OH)₂D₃, T helper cells may increase, and allergic response also increases. As allergic events increased, these children did not go outside and thus lacked sun exposure. This vicious cycle must be broken, and children with RT + AR should have sunlight exposure to increase 1,25(OH)₂D₃ levels.
Vitamin D: Pathophysiology and clinical applicability in paediatrics
2012, Anales de Pediatria
La vitamina D se ha relacionado siempre con el metabolismo fosfocálcico, pero se han encontrado receptores de la vitamina D o de sus metabolitos en diferentes células del organismo, lo que indica que puede estar implicada en otros mecanismos fisiológicos. El déficit de vitamina D se ha relacionado con un mayor riesgo de infecciones, enfermedades autoinmunitarias, diabetes, síndrome metabólico, obesidad, asma y ciertas enfermedades neurológicas, como la esquizofrenia.
Actualmente existen diferentes técnicas para la determinación del 25(OH) colecalciferol en sangre y hay discrepancias entre ellas en cuanto a los resultados obtenidos en una misma muestra. Es importante conseguir una uniformización de las técnicas que permitan estudios de investigación comparables.
Todavía no se han establecido los valores adecuados de vitamina D en el organismo que aseguren todas sus funciones, pero se considera que no debe ser inferior a 20 ng/ml (50 nml/l), estando en discusión cómo conseguir estos niveles mínimos en toda la población. Dado que la principal fuente de vitamina D es la irradiación solar, hay que buscar estrategias que no entren en contradicción con los mensajes de prevención del cáncer de piel. En los últimos años se han producido variaciones en cuanto las recomendaciones de ingesta de vitamina D que implican a las actividades profilácticas que se realizan en el ámbito de la atención primaria.
Este texto revisa la fisiología, las acciones, la determinación de laboratorio, los niveles deseables en el organismo y las recomendaciones de ingesta de la vitamina D, y resalta las numerosas cuestiones que plantean nuevas investigaciones.
Vitamin D has always been associated with calcium –phosphate metabolism, but vitamin D receptors or its metabolites have been found in different body cells, indicating a possible involvement in other physiological mechanisms. Vitamin D deficiency has been associated with an increased risk of infections, autoimmune diseases, diabetes, metabolic syndrome, obesity, asthma and certain neurological diseases such as schizophrenia.
Currently there are different techniques for measuring 25 (OH) cholecalciferol in blood, but the results are variable and controversial. It is important to achieve standardization of these techniques to be able to compare the results obtained in different studies.
Normal physiological vitamin D levels have not yet been established, but they must be higher than 20 ng/ml (50 nmol/l) in order to perform it physiological function. It is still under discussion on how to achieve these minimum levels. Since the main source of vitamin D is sunlight, we should look for strategies that do not contradict the messages of prevention of skin cancer. In recent years, recommendations for vitamin D intake have changed, involving prophylactic activities carried out in Primary Care.
This manuscript reviews the physiology, actions, laboratory determination, desirable levels, and vitamin D intake recommendations, and it highlights many questions raised by new research.
The association between vitamin D levels and recurrent group A streptococcal tonsillopharyngitis in adults
2012, International Journal of Infectious Diseases
Citation Excerpt :
Moreover, scientific evidence shows the important role of vitamin D in the immune system.19,20 The antimicrobial peptides (AMPs) defensin and cathelicidin, which are the principal defense factors of the upper respiratory tract (URT), are upregulated by vitamin D.21,22 Aydin et al. showed that vitamin D insufficiency was more prevalent in children with recurrent tonsillitis than in healthy children.23 Despite the fact that such an association between vitamin D deficiency and the susceptibility to infections of the respiratory tract has been suggested for many years, to the best of our knowledge no such evidence-based study had been undertaken in adults.
To determine the association between recurrent group A streptococcal (GAS) tonsillopharyngitis and serum 25-hydroxy (25(OH)) vitamin D among adult subjects.
Adult patients with tonsillopharyngitis between January 2007 and December 2009 were reviewed and identified retrospectively. Cases with a medical history of recurrent GAS tonsillopharyngitis were compared to age- and gender-matched individuals without a medical history of GAS tonsillopharyngitis. Recurrent tonsillopharyngitis was defined as three or more episodes of GAS tonsillopharyngitis per year for a period of two consecutive years.
Fifty-four cases with recurrent GAS tonsillopharyngitis and 50 controls were enrolled. There were no significant differences between cases and controls with regard to mean age (41 ± 13 vs. 42 ± 12 years; p = 0.7) and male gender (55% vs. 54%; p = 0.6). Mean serum levels of 25(OH) vitamin D among subjects with recurrent GAS tonsillopharyngitis were significantly lower from the controls (11.5 ng/ml ± 4.7 vs. 26 ng/ml ± 7; p = 0.001). Multiple regression analysis showed that a serum 25(OH) vitamin D level <20 ng/ml was associated with recurrent GAS tonsillopharyngitis (odds ratio 1.62, 95% confidence interval 1.51–1.76; p < 0.001).
Our findings indicate a link between vitamin D deficiency and the recurrence of GAS tonsillopharyngitis.
Manganese-superoxide dismutase and glutathione peroxidase 1 polymorphisms in recurrent tonsillitis and tonsillar hypertrophy
2012, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
MBL, which activates the complement system, is an important molecule in the immune system. In another study, the vitamin D receptor gene polymorphism was researched by comparing RT and control groups, however, no significant difference was found between the groups [24]. In conclusion, as genetic predisposition is one factor that causes a tendency towards tonsillar disease, we have investigated the MnSOD Ala-9Val and the GPx1 Pro198Leu polymorphisms in patients with RT and TH, a subject never previously researched.
To investigate the association of manganese-superoxide dismutase and glutathione peroxidase 1 polymorphisms with susceptibility to recurrent tonsillitis and tonsillar hypertrophy.
The study consisted of 103 patients with recurrent tonsillitis, 105 patients with tonsillar hypertrophy and 106 control subjects with similar age and sex. Genomic DNA was extracted from peripheral leukocytes of whole blood which were obtained from all patients and control subjects. Genotyping was performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms by a method based on PCR amplification and detection of polymorphisms with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies were compared between patients with recurrent tonsillitis and tonsillar hypertrophy and 106 healthy control subjects.
The genotype distribution of the MnSOD Ala-9Val single nucleotide polymorphism was significantly different for the controls and the recurrent tonsillitis patients (P = 0.009). Whereas, no significant difference was found between the patients with tonsillar hypertrophy and the control group (P = 0.369). The frequency of the MnSOD CC genotype was lower, and that of the T allele was significantly higher, in recurrent tonsillitis patients than in control subjects. In addition, the frequency of tonsillitis was significantly higher in recurrent tonsillitis patients with the MnSOD Ala-9Val polymorphism than the patients with wild-type (P = 0.008). Also, no significant difference was found between patient groups and control subjects in the distribution of the genotype and allele frequency of the GPx1 Pro198Leu single nucleotide polymorphism.
The MnSOD Ala-9Val polymorphism causes susceptibility to recurrent tonsillitis in Turkish children. And we suggest that there may be a possible relation between local and recurrent infections or inflammation of the tonsillar tissue and the MnSOD Ala-9Val single nucleotide polymorphism in pediatric patients with RT.
Association between serum 25-hydroxyvitamin D concentration and symptoms of respiratory tract infection in a Norwegian population: The Tromso Study
2014, Public Health Nutrition
Impact of Interleukin-37 and Vitamin D on children with Streptococcus pyogenes sore throat in Salah al-Din Governorate, Iraq
2024, Journal of Applied and Natural Science

View all citing articles on Scopus

View full text

Vitamin D levels in children with recurrent tonsillitis

Abstract

Aim

Methods

Results

Conclusion

Introduction

Section snippets

Study design

The eligibility criteria for participants

Results

Discussion

Acknowledgement

Int. J. Pediatr. Otorhinolaryngol.

J. Steroid Biochem. Mol. Biol.

Gene

J. Steroid Biochem. Mol. Biol.

Mol. Immunol.

Ann. Epidemiol.

J. Nutr.

Clin. Lab. Med.

Endocrinol. Metab. Clin. N. Am.

Bacteriology of normal and diseased tonsils assessed by fine-needle aspiration: haemophilus influenzae and the pathogenesis of recurrent acute tonsillitis

Clin. Otolaryngol. Allied Sci.