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Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity

Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity
Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity
Background

Asthma is characterized by airflow limitation and airway reactivity (AR). Interleukin-13 (IL-13) is involved in the pathogenesis of asthma. Two functional SNPs, rs20541 and rs1800925, of the IL-13 gene (IL13) have been frequently associated with asthma-related lung functions. However, genetic variation alone does not fully explain asthma risk. DNA-methylation (DNA-M) is an epigenetic mechanism that regulates gene expression and can be influenced by both environment and genetic variants. To explore the interplay of prenatal maternal smoking, genetic variants and DNA-M, we used a two-stage model: (1) identifying cytosine phosphate guanine (CpG) sites where DNA-M is influenced by the interaction between genetic variants and maternal smoking during pregnancy (conditional methQTL (methylation quantitative trait loci)); and (2) determining the effect of the interaction between DNA-M of CpG (from stage 1) and SNPs (modifying genetic variants; modGV) on airflow limitation and AR in 245 female participants of the Isle of Wight birth cohort. DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.

Findings

Six CpG sites were analyzed in stage 1. DNA-M at cg13566430 was influenced by interaction of maternal smoking during pregnancy and rs20541. In stage 2, genotype at rs1800925 interacted with DNA-M at cg13566430 significantly affecting airflow limitation (P?=?0.042) and AR (P?=?0.01).

Conclusion

Both genetic variants and environment affect DNA-M. This study supports the proposed two-stage model (methQTL and modGV) to study genetic variants, environment and DNA-M interactions in asthma-related lung function.
asthma genetics and epigenetics, airway reactivity, DNA methylation, IL13 gene, lung functions, maternal smoking during pregnancy
1868-7075
1-6
Patil, Veeresh K
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Soto-Ramirez, Nelis
4cfdc4e4-8727-4cf9-95bb-e31845c373e4
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, S Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Patil, Veeresh K
b898b9a7-db31-4c1c-b0f0-4165b3e4d29c
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Soto-Ramirez, Nelis
4cfdc4e4-8727-4cf9-95bb-e31845c373e4
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, S Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Patil, Veeresh K, Holloway, John W, Zhang, Hongmei, Soto-Ramirez, Nelis, Ewart, Susan, Arshad, S Hasan and Karmaus, Wilfried (2013) Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity. Clinical Epigenetics, 5 (1), 1-6. (doi:10.1186/1868-7083-5-22).

Record type: Article

Abstract

Background

Asthma is characterized by airflow limitation and airway reactivity (AR). Interleukin-13 (IL-13) is involved in the pathogenesis of asthma. Two functional SNPs, rs20541 and rs1800925, of the IL-13 gene (IL13) have been frequently associated with asthma-related lung functions. However, genetic variation alone does not fully explain asthma risk. DNA-methylation (DNA-M) is an epigenetic mechanism that regulates gene expression and can be influenced by both environment and genetic variants. To explore the interplay of prenatal maternal smoking, genetic variants and DNA-M, we used a two-stage model: (1) identifying cytosine phosphate guanine (CpG) sites where DNA-M is influenced by the interaction between genetic variants and maternal smoking during pregnancy (conditional methQTL (methylation quantitative trait loci)); and (2) determining the effect of the interaction between DNA-M of CpG (from stage 1) and SNPs (modifying genetic variants; modGV) on airflow limitation and AR in 245 female participants of the Isle of Wight birth cohort. DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.

Findings

Six CpG sites were analyzed in stage 1. DNA-M at cg13566430 was influenced by interaction of maternal smoking during pregnancy and rs20541. In stage 2, genotype at rs1800925 interacted with DNA-M at cg13566430 significantly affecting airflow limitation (P?=?0.042) and AR (P?=?0.01).

Conclusion

Both genetic variants and environment affect DNA-M. This study supports the proposed two-stage model (methQTL and modGV) to study genetic variants, environment and DNA-M interactions in asthma-related lung function.

Text
Patil VK et al 2013 Clin Epigenet Interaction of prenatal maternal smoking interleukin 13 genetic variants and DNA methylation influencing airflow and ai.pdf - Version of Record
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More information

Published date: 6 December 2013
Keywords: asthma genetics and epigenetics, airway reactivity, DNA methylation, IL13 gene, lung functions, maternal smoking during pregnancy
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 360472
URI: http://eprints.soton.ac.uk/id/eprint/360472
ISSN: 1868-7075
PURE UUID: b72b88fd-7cf4-4149-bce6-62239de7152f
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 10 Dec 2013 14:24
Last modified: 28 Oct 2023 01:42

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Contributors

Author: Veeresh K Patil
Author: John W Holloway ORCID iD
Author: Hongmei Zhang
Author: Nelis Soto-Ramirez
Author: Susan Ewart
Author: S Hasan Arshad
Author: Wilfried Karmaus

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