Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Predisposition to childhood otitis media and genetic polymorphisms within the toll-like receptor 4 (TLR4) Locus

Hafren, L and Einarsdottir, E and Kentala, E and Hammaren-Malmi, S and Bhutta, MF and MacArthur, CJ and Wilmot, B and Casselbrant, M and Conley, YP and Weeks, DE and Mandel, EM and Vaarala, O and Kallio, A and Melin, M and Nieminen, JK and Leinonen, E and Kere, J and Mattila, PS (2015) Predisposition to childhood otitis media and genetic polymorphisms within the toll-like receptor 4 (TLR4) Locus. PLoS ONE, 10 (7).

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (344kB)
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

© 2015 Hafrén et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFá secretion in myeloid dendritic cells. Conclusions The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hafren, L
Einarsdottir, E
Kentala, E
Hammaren-Malmi, S
Bhutta, MF
MacArthur, CJ
Wilmot, B
Casselbrant, Mcasselm@pitt.eduCASSELM
Conley, YPyconley@pitt.eduYCONLEY
Weeks, DEweeks@pitt.eduWEEKS0000-0001-9410-7228
Mandel, EMmandele@pitt.eduMANDELE
Vaarala, O
Kallio, A
Melin, M
Nieminen, JK
Leinonen, E
Kere, J
Mattila, PS
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorYao, Yong-GangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 15 July 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0132551
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
School of Medicine > Otolaryngology
School of Nursing > Nursing
Refereed: Yes
Date Deposited: 23 Aug 2016 14:24
Last Modified: 23 Jun 2018 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/28418

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item