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Changes in DNA methylation from age 18 to pregnancy in Type 1, 2, and 17 T Hhelper and regulatory T-cells pathway genes

Changes in DNA methylation from age 18 to pregnancy in Type 1, 2, and 17 T Hhelper and regulatory T-cells pathway genes
Changes in DNA methylation from age 18 to pregnancy in Type 1, 2, and 17 T Hhelper and regulatory T-cells pathway genes
To succeed, pregnancies need to initiate immune biases towards T helper 2 (Th2) responses, yet little is known about what establishes this bias. Using the Illumina 450 K platform, we explored changes in DNA methylation (DNAm) of Th1, Th2, Th17, and regulatory T cell pathway genes before and during pregnancy. Female participants were recruited at birth (1989), and followed through age 18 years and their pregnancy (2011–2015). Peripheral blood DNAm was measured in 245 girls at 18 years; from among these girls, the DNAm of 54 women was repeatedly measured in the first (weeks 8–21, n = 39) and second (weeks 22–38, n = 35) halves of pregnancy, respectively. M-values (logit-transformed β-values of DNAm) were analyzed: First, with repeated measurement models, cytosine–phosphate–guanine sites (CpGs) of pathway genes in pregnancy and at age 18 (nonpregnant) were compared for changes (p ≤ 0.05). Second, we tested how many of the 348 pathway-related CpGs changed compared to 10 randomly selected subsets of all other CpGs and compared to 10 randomly selected subsets of other CD4+-related CpGs (348 in each subset). Contrasted to the nonpregnant state, 27.7% of Th1-related CpGs changed in the first and 36.1% in the second half of pregnancy. Among the Th2 pathway CpGs, proportions of changes were 35.1% (first) and 33.8% (second half). The methylation changes suggest involvement of both Th1 and Th2 pathway CpGs in the immune bias during pregnancy. Changes in regulatory T cell and Th17 pathways need further exploration
1422-0067
477
Iqbal, Sabrina
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Lockett, Gabrielle
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Holloway, John
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Arshad, S.
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Tetali, Sabarinath
fde79d61-98f3-4629-9eed-841d9725ef7d
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Iqbal, Sabrina
ae6751d8-f4e6-4798-a60d-209aba196763
Lockett, Gabrielle
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Arshad, S.
917e246d-2e60-472f-8d30-94b01ef28958
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
Tetali, Sabarinath
fde79d61-98f3-4629-9eed-841d9725ef7d
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Iqbal, Sabrina, Lockett, Gabrielle, Holloway, John, Arshad, S., Zhang, Hongmei, Kaushal, Akhilesh, Tetali, Sabarinath, Mukherjee, Nandini and Karmaus, Wilfried (2018) Changes in DNA methylation from age 18 to pregnancy in Type 1, 2, and 17 T Hhelper and regulatory T-cells pathway genes. International Journal of Molecular Sciences, 19 (2), 477. (doi:10.3390/ijms19020477).

Record type: Article

Abstract

To succeed, pregnancies need to initiate immune biases towards T helper 2 (Th2) responses, yet little is known about what establishes this bias. Using the Illumina 450 K platform, we explored changes in DNA methylation (DNAm) of Th1, Th2, Th17, and regulatory T cell pathway genes before and during pregnancy. Female participants were recruited at birth (1989), and followed through age 18 years and their pregnancy (2011–2015). Peripheral blood DNAm was measured in 245 girls at 18 years; from among these girls, the DNAm of 54 women was repeatedly measured in the first (weeks 8–21, n = 39) and second (weeks 22–38, n = 35) halves of pregnancy, respectively. M-values (logit-transformed β-values of DNAm) were analyzed: First, with repeated measurement models, cytosine–phosphate–guanine sites (CpGs) of pathway genes in pregnancy and at age 18 (nonpregnant) were compared for changes (p ≤ 0.05). Second, we tested how many of the 348 pathway-related CpGs changed compared to 10 randomly selected subsets of all other CpGs and compared to 10 randomly selected subsets of other CD4+-related CpGs (348 in each subset). Contrasted to the nonpregnant state, 27.7% of Th1-related CpGs changed in the first and 36.1% in the second half of pregnancy. Among the Th2 pathway CpGs, proportions of changes were 35.1% (first) and 33.8% (second half). The methylation changes suggest involvement of both Th1 and Th2 pathway CpGs in the immune bias during pregnancy. Changes in regulatory T cell and Th17 pathways need further exploration

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Accepted/In Press date: 1 February 2018
e-pub ahead of print date: 6 February 2018

Identifiers

Local EPrints ID: 417841
URI: http://eprints.soton.ac.uk/id/eprint/417841
ISSN: 1422-0067
PURE UUID: e76b1eb5-61ad-432d-85b8-14d735355ef6
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 15 Feb 2018 17:30
Last modified: 18 Feb 2021 16:49

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