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DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age

DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age
DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age
The leptin gene (LEP) plays a regulatory role in satiety, inflammation, and allergy. Prior findings linking leptin to asthma motivated us to investigate whether DNA methylation (DNA-M) of CpG (cytosine-phosphate-guanine) sites in concert with single nucleotide polymorphisms (SNPs) of LEP can explain the risk of asthma and lung function. Methylation of CpG sites was assessed using the Illumina Infinium Human Methylation 450 beadchip in blood samples collected from 10- and 18-year-old boys and girls from the Isle of Wight (IOW) birth cohort (UK). Four LEP SNPs were genotyped. Linear and log linear models were used for the analysis, adjusting for false discovery rate (FDR). The analyses were repeated in the BAMSE cohort (Sweden). In the IOW study, the interaction of cg00666422 and rs11763517 (CT vs TT and CC) was associated with FEV1 (FDR-adjusted p-value: 0.03), FEV1/FVC ratio (FDR- adjusted p-value: 0.0096), and FEF25-75% (FDR-adjusted p-value: 0.00048) such that they decreased with increasing DNA-M. The interaction of the same CpG-SNP pair was also associated with increased risk of asthma at age 18. We replicated the findings for FEV1/FVC and FEF25-75% in a smaller sample of 34 participants at age 10. Regarding the BAMSE cohort, although, the interaction of cg00666422 and rs11763517 on lung function were not significant, the direction of the effect was the same as in IOW cohort. Thus, penetrance of LEP genotype seems to be modified by methylation at cg00666422 and is linked to airway obstruction and asthma.
1-17
Mukherjee, Nadini
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Lockett, Gabrielle A.
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Merid, Simon K.
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Melén, Eric
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Pershagen, Göran
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Holloway, John
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Arshad, Syed Hasan
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Ewart, Susan
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Zhang, Hongmei
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Karmaus, Wilfried
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Mukherjee, Nadini
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Lockett, Gabrielle A.
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Merid, Simon K.
c7eb7686-d1e1-45ed-93e3-e9f3e85ce197
Melén, Eric
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Pershagen, Göran
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Holloway, John
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Arshad, Syed Hasan
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Ewart, Susan
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Zhang, Hongmei
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Karmaus, Wilfried
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Mukherjee, Nadini, Lockett, Gabrielle A., Merid, Simon K., Melén, Eric, Pershagen, Göran, Holloway, John, Arshad, Syed Hasan, Ewart, Susan, Zhang, Hongmei and Karmaus, Wilfried (2016) DNA methylation and genetic polymorphisms of the Leptin gene interact to influence lung function outcomes and asthma at 18 years of age. International Journal of Molecular Epidemiology and Genetics, 7 (1), 1-17.

Record type: Article

Abstract

The leptin gene (LEP) plays a regulatory role in satiety, inflammation, and allergy. Prior findings linking leptin to asthma motivated us to investigate whether DNA methylation (DNA-M) of CpG (cytosine-phosphate-guanine) sites in concert with single nucleotide polymorphisms (SNPs) of LEP can explain the risk of asthma and lung function. Methylation of CpG sites was assessed using the Illumina Infinium Human Methylation 450 beadchip in blood samples collected from 10- and 18-year-old boys and girls from the Isle of Wight (IOW) birth cohort (UK). Four LEP SNPs were genotyped. Linear and log linear models were used for the analysis, adjusting for false discovery rate (FDR). The analyses were repeated in the BAMSE cohort (Sweden). In the IOW study, the interaction of cg00666422 and rs11763517 (CT vs TT and CC) was associated with FEV1 (FDR-adjusted p-value: 0.03), FEV1/FVC ratio (FDR- adjusted p-value: 0.0096), and FEF25-75% (FDR-adjusted p-value: 0.00048) such that they decreased with increasing DNA-M. The interaction of the same CpG-SNP pair was also associated with increased risk of asthma at age 18. We replicated the findings for FEV1/FVC and FEF25-75% in a smaller sample of 34 participants at age 10. Regarding the BAMSE cohort, although, the interaction of cg00666422 and rs11763517 on lung function were not significant, the direction of the effect was the same as in IOW cohort. Thus, penetrance of LEP genotype seems to be modified by methylation at cg00666422 and is linked to airway obstruction and asthma.

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More information

Accepted/In Press date: 28 February 2016
Published date: 30 March 2016
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 390707
URI: https://eprints.soton.ac.uk/id/eprint/390707
PURE UUID: e6d33cc2-eef1-4c69-ba82-5990d5e9b9c2
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 07 Apr 2016 15:46
Last modified: 03 Dec 2019 01:58

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Contributors

Author: Nadini Mukherjee
Author: Gabrielle A. Lockett
Author: Simon K. Merid
Author: Eric Melén
Author: Göran Pershagen
Author: John Holloway ORCID iD
Author: Susan Ewart
Author: Hongmei Zhang
Author: Wilfried Karmaus

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