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Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence

Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence
Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence
Background

Vaccinations have been suggested to be associated with increased risk of allergic diseases. Tetanus vaccination is one of the most frequently administered vaccines as a part of wound management and was also found to be associated with increased serum IgE levels. We hypothesized that the vaccination modifies the risk of allergic diseases through epigenetic changes such as DNA methylation.

Method

Data on tetanus vaccination between 10 and 18 years of age was collected from a birth cohort established on the Isle of Wight UK in 1989. DNA methylation data were collected from individuals at different ages (at birth [n = 30], age 10 [n = 34], age 18 [n = 245] and during pregnancy [n = 121]) using the Illumina Infinium HumanMethylation450 K array. Firstly, we performed an epigenome-wide screening to identify cytosine-phosphate-guanine sites (CpGs) associated with tetanus vaccination in 18-year-olds. Secondly, we tested their association with asthma, allergic sensitization, eczema, serum IgE and pulmonary lung function (FVC, FEV1, FEV1/FVC, and FEF25-75%). We then described changes in the methylation of the selected CpG sites over age, and by vaccination status.

Results

Tetanus vaccination was found to be associated with decreased methylation of cg14472551 (p value 0.5 × 10?5, FDR-adjusted p value 2.1 × 10?4) and increased methylation of cg01669161 (p value 0.0007, FDR-adjusted p value 0.014). Both CpGs, in turn, were associated with decreased risk of asthma at 18 years of age. Cg14472551 is located in an intron of KIAA1549L, whose protein binds to a B-cell commitment transcription factor; cg01669161 is located between an antisense regulator of the proteasome assembly chaperone PSMG3, and TFAMP1, a pseudogene. Increased methylation of cg01669161 was also associated with decreased serum IgE levels.

Conclusion

DNA methylation changes following tetanus vaccination may offer a novel prospect to explain a differential occurrence of asthma in adolescence.
6493-6501
Janjanam, Vimala Devi
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Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Kurukulaaratchy, Ramesh
57cf8bbb-7cd2-478e-9b8b-6ebfa27e806b
Mitchell, Frances
fb4be2d3-544e-49ce-912e-c5f0f9553a01
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Janjanam, Vimala Devi
62f16860-3d75-4efc-b6b6-2a3a88549a85
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Kurukulaaratchy, Ramesh
57cf8bbb-7cd2-478e-9b8b-6ebfa27e806b
Mitchell, Frances
fb4be2d3-544e-49ce-912e-c5f0f9553a01
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Janjanam, Vimala Devi, Mukherjee, Nandini, Lockett, Gabrielle A., Rezwan, Faisal I., Kurukulaaratchy, Ramesh, Mitchell, Frances, Zhang, Hongmei, Arshad, Hasan, Holloway, John and Karmaus, Wilfried (2016) Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence. Vaccine, 34 (51), 6493-6501. (doi:10.1016/j.vaccine.2016.10.068). (PMID:27866770)

Record type: Article

Abstract

Background

Vaccinations have been suggested to be associated with increased risk of allergic diseases. Tetanus vaccination is one of the most frequently administered vaccines as a part of wound management and was also found to be associated with increased serum IgE levels. We hypothesized that the vaccination modifies the risk of allergic diseases through epigenetic changes such as DNA methylation.

Method

Data on tetanus vaccination between 10 and 18 years of age was collected from a birth cohort established on the Isle of Wight UK in 1989. DNA methylation data were collected from individuals at different ages (at birth [n = 30], age 10 [n = 34], age 18 [n = 245] and during pregnancy [n = 121]) using the Illumina Infinium HumanMethylation450 K array. Firstly, we performed an epigenome-wide screening to identify cytosine-phosphate-guanine sites (CpGs) associated with tetanus vaccination in 18-year-olds. Secondly, we tested their association with asthma, allergic sensitization, eczema, serum IgE and pulmonary lung function (FVC, FEV1, FEV1/FVC, and FEF25-75%). We then described changes in the methylation of the selected CpG sites over age, and by vaccination status.

Results

Tetanus vaccination was found to be associated with decreased methylation of cg14472551 (p value 0.5 × 10?5, FDR-adjusted p value 2.1 × 10?4) and increased methylation of cg01669161 (p value 0.0007, FDR-adjusted p value 0.014). Both CpGs, in turn, were associated with decreased risk of asthma at 18 years of age. Cg14472551 is located in an intron of KIAA1549L, whose protein binds to a B-cell commitment transcription factor; cg01669161 is located between an antisense regulator of the proteasome assembly chaperone PSMG3, and TFAMP1, a pseudogene. Increased methylation of cg01669161 was also associated with decreased serum IgE levels.

Conclusion

DNA methylation changes following tetanus vaccination may offer a novel prospect to explain a differential occurrence of asthma in adolescence.

Other
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More information

Accepted/In Press date: 26 October 2016
e-pub ahead of print date: 17 November 2016
Published date: 12 December 2016
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 403105
URI: https://eprints.soton.ac.uk/id/eprint/403105
PURE UUID: d12ef9ba-8526-4c67-a1ce-b0adf2e9e1e5
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 21 Nov 2016 15:32
Last modified: 29 Oct 2019 02:01

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Contributors

Author: Vimala Devi Janjanam
Author: Nandini Mukherjee
Author: Gabrielle A. Lockett
Author: Ramesh Kurukulaaratchy
Author: Frances Mitchell
Author: Hongmei Zhang
Author: Hasan Arshad
Author: John Holloway ORCID iD
Author: Wilfried Karmaus

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