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|a Patil, Veeresh K
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|a Holloway, John W
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|a Zhang, Hongmei
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|a Soto-Ramirez, Nelis
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|a Ewart, Susan
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|a Arshad, S Hasan
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|a Karmaus, Wilfried
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|a Interaction of prenatal maternal smoking, interleukin 13 genetic variants and DNA methylation influencing airflow and airway reactivity
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|c 2013-12-06.
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|z Get fulltext
|u https://eprints.soton.ac.uk/360472/1/Patil%2520VK%2520et%2520al%25202013%2520Clin%2520Epigenet%2520Interaction%2520of%2520prenatal%2520maternal%2520smoking%2520interleukin%252013%2520genetic%2520variants%2520and%2520DNA%2520methylation%2520influencing%2520airflow%2520and%2520ai.pdf
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|a 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.
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