Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media

Janak Patel, Sangeeta Nair, Krystal Revai, James Grady, Kokab Saeed, Reuben Matalon, Stan Block, Tasnee Chonmaitree

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-α-308, interleukin-1β+3953, and interleukin-6-174, in susceptibility to recurrent otitis media in childhood. METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-α-308 and interleukin-6 -174 heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-α-308 and interleukin-6-174 polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-α-308 polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-α-308 and interleukin-6 -174 polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.

Original languageEnglish (US)
Pages (from-to)2273-2279
Number of pages7
JournalPediatrics
Volume118
Issue number6
DOIs
StatePublished - Dec 2006

Fingerprint

Otitis Media
Cytokines
Genes
Tumor Necrosis Factor-alpha
Interleukin-6
Middle Ear Ventilation
Genotype
Single Nucleotide Polymorphism
Breast Feeding
Interleukin-1
Smoke
Tobacco Products
Restriction Fragment Length Polymorphisms
DNA

Keywords

  • Acute-phase cytokines
  • Gene polymorphism
  • Otitis media

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Patel, J., Nair, S., Revai, K., Grady, J., Saeed, K., Matalon, R., ... Chonmaitree, T. (2006). Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. Pediatrics, 118(6), 2273-2279. https://doi.org/10.1542/peds.2006-0764

Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. / Patel, Janak; Nair, Sangeeta; Revai, Krystal; Grady, James; Saeed, Kokab; Matalon, Reuben; Block, Stan; Chonmaitree, Tasnee.

In: Pediatrics, Vol. 118, No. 6, 12.2006, p. 2273-2279.

Research output: Contribution to journalArticle

Patel, J, Nair, S, Revai, K, Grady, J, Saeed, K, Matalon, R, Block, S & Chonmaitree, T 2006, 'Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media', Pediatrics, vol. 118, no. 6, pp. 2273-2279. https://doi.org/10.1542/peds.2006-0764
Patel, Janak ; Nair, Sangeeta ; Revai, Krystal ; Grady, James ; Saeed, Kokab ; Matalon, Reuben ; Block, Stan ; Chonmaitree, Tasnee. / Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media. In: Pediatrics. 2006 ; Vol. 118, No. 6. pp. 2273-2279.
@article{febe577bbfb4471d9014d178411c1fe6,
title = "Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media",
abstract = "OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-α-308, interleukin-1β+3953, and interleukin-6-174, in susceptibility to recurrent otitis media in childhood. METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-α-308 and interleukin-6 -174 heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-α-308 and interleukin-6-174 polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-α-308 polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-α-308 and interleukin-6 -174 polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.",
keywords = "Acute-phase cytokines, Gene polymorphism, Otitis media",
author = "Janak Patel and Sangeeta Nair and Krystal Revai and James Grady and Kokab Saeed and Reuben Matalon and Stan Block and Tasnee Chonmaitree",
year = "2006",
month = "12",
doi = "10.1542/peds.2006-0764",
language = "English (US)",
volume = "118",
pages = "2273--2279",
journal = "Pediatrics",
issn = "0031-4005",
publisher = "American Academy of Pediatrics",
number = "6",

}

TY - JOUR

T1 - Association of proinflammatory cytokine gene polymorphisms with susceptibility to otitis media

AU - Patel, Janak

AU - Nair, Sangeeta

AU - Revai, Krystal

AU - Grady, James

AU - Saeed, Kokab

AU - Matalon, Reuben

AU - Block, Stan

AU - Chonmaitree, Tasnee

PY - 2006/12

Y1 - 2006/12

N2 - OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-α-308, interleukin-1β+3953, and interleukin-6-174, in susceptibility to recurrent otitis media in childhood. METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-α-308 and interleukin-6 -174 heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-α-308 and interleukin-6-174 polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-α-308 polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-α-308 and interleukin-6 -174 polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.

AB - OBJECTIVE. Susceptibility to otitis media results from complex interactions among genetic factors of the host, exposure to pathogens, and environmental influences. The objective of this study was to study the role of single-nucleotide polymorphisms of regulatory elements of proinflammatory cytokine genes tumor necrosis factor-α-308, interleukin-1β+3953, and interleukin-6-174, in susceptibility to recurrent otitis media in childhood. METHODS. A total of 505 children (296 otitis media susceptible, 209 nonsusceptible as control) were enrolled at 2 sites (Texas and Kentucky). DNA of the children was studied for specific single-nucleotide polymorphisms by restriction fragment length polymorphism assay and confirmed by gene sequencing. RESULTS. In the overall study group, tumor necrosis factor-α-308 and interleukin-6 -174 heterozygous or homozygous polymorphisms (high cytokine-producing genotypes) were significantly associated with otitis media susceptibility. The same association was found in a match-paired subgroup of 384 subjects. In the overall study group, there was a significant step-wise increase in otitis media susceptibility with increasing number of concomitant polymorphic genotypes. Simultaneous combination of tumor necrosis factor-α-308 and interleukin-6-174 polymorphisms further increased the risk for otitis media susceptibility. These 2 polymorphic genotypes also were associated with the increased risk for tympanostomy tube placement. Children who had tumor necrosis factor-α-308 polymorphism and were breastfed for <1 month or exposed to cigarette smoke were more likely to be otitis media susceptible. CONCLUSIONS. Our data suggest that tumor necrosis factor-α-308 and interleukin-6 -174 polymorphisms are associated with increased risk for otitis media susceptibility and placement of tympanostomy tubes. Environmental factors such as breastfeeding may modify the risk for otitis media susceptibility in polymorphic individuals.

KW - Acute-phase cytokines

KW - Gene polymorphism

KW - Otitis media

UR - http://www.scopus.com/inward/record.url?scp=33947121641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947121641&partnerID=8YFLogxK

U2 - 10.1542/peds.2006-0764

DO - 10.1542/peds.2006-0764

M3 - Article

VL - 118

SP - 2273

EP - 2279

JO - Pediatrics

JF - Pediatrics

SN - 0031-4005

IS - 6

ER -