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The methylation of the LEPR/LEPROT genotype at the promoter and body regions influence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy

The methylation of the LEPR/LEPROT genotype at the promoter and body regions influence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy
The methylation of the LEPR/LEPROT genotype at the promoter and body regions influence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy

To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links gestational smoking and leptin serum levels and BMI later in life, we focused on female offspring, 18 years of age, from the Isle of Wight Birth Cohort (IOWBC). Leptin binds to the leptin receptor encoded by the LEPR/LEPROT genotype. Using general linear models, we tested a two-stage model. First, we investigated whether single nucleotide polymorphisms (SNPs) acting as methylation quantitative trait loci (methQTLs) depending on gestational smoking were related to differentially methylated cytosine-phosphate-guanine (CpG) sites. In stage 2, we tested whether the selected CpG sites, in interaction with other SNPs (modifiable genetic variants, modGV), are associated with serum leptin and BMI (stage 2). Children from the IOWBC were followed from birth to age 18. Information on gestational smoking was gathered upon delivery. SNPs tagging LEPR and LEPROT genes were genotyped. Data on LEPR/LEPROTDNA-M and leptin were obtained from blood samples drawn at age 18; to determine BMI, height and weight were ascertained. Blood samples were provided by 238 girls. Of the 21 CpG sites, interactions between gestational smoking and SNPs were detected for 16 CpGs. Methylation of seven of the 16 CpGs were, in interaction with modGVs, associated with leptin levels at age 18 years. Two CpGs survived a multiple testing penalty and were also associated with BMI. This two-stage model may explain why maternal smoking has a long-term effect on leptin levels and BMI in girls at age 18 years.

Journal Article
86-100
Yousefi, Mitra
9d5d6aa8-bba4-40b0-861e-0b60ceaea587
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Yousefi, Mitra
9d5d6aa8-bba4-40b0-861e-0b60ceaea587
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Yousefi, Mitra, Karmaus, Wilfried, Zhang, Hongmei, Ewart, Susan, Arshad, Hasan and Holloway, John W (2013) The methylation of the LEPR/LEPROT genotype at the promoter and body regions influence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy. International Journal of Molecular Epidemiology and Genetics, 4 (2), 86-100.

Record type: Article

Abstract

To determine whether DNA methylation (DNA-M) of the leptin receptor genotype (LEPR/LEPROT) links gestational smoking and leptin serum levels and BMI later in life, we focused on female offspring, 18 years of age, from the Isle of Wight Birth Cohort (IOWBC). Leptin binds to the leptin receptor encoded by the LEPR/LEPROT genotype. Using general linear models, we tested a two-stage model. First, we investigated whether single nucleotide polymorphisms (SNPs) acting as methylation quantitative trait loci (methQTLs) depending on gestational smoking were related to differentially methylated cytosine-phosphate-guanine (CpG) sites. In stage 2, we tested whether the selected CpG sites, in interaction with other SNPs (modifiable genetic variants, modGV), are associated with serum leptin and BMI (stage 2). Children from the IOWBC were followed from birth to age 18. Information on gestational smoking was gathered upon delivery. SNPs tagging LEPR and LEPROT genes were genotyped. Data on LEPR/LEPROTDNA-M and leptin were obtained from blood samples drawn at age 18; to determine BMI, height and weight were ascertained. Blood samples were provided by 238 girls. Of the 21 CpG sites, interactions between gestational smoking and SNPs were detected for 16 CpGs. Methylation of seven of the 16 CpGs were, in interaction with modGVs, associated with leptin levels at age 18 years. Two CpGs survived a multiple testing penalty and were also associated with BMI. This two-stage model may explain why maternal smoking has a long-term effect on leptin levels and BMI in girls at age 18 years.

Text
The methylation of the LEPR/LEPROT genotype at the promoter and body regions in uence concentrations of leptin in girls and BMI at age 18 years if their mother smoked during pregnancy
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More information

Accepted/In Press date: 15 June 2013
e-pub ahead of print date: 25 June 2013
Published date: 30 June 2013
Keywords: Journal Article
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 409428
URI: http://eprints.soton.ac.uk/id/eprint/409428
PURE UUID: 50be4d5b-3fcc-4900-ae43-06f0d3d3c111
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 28 May 2017 04:09
Last modified: 28 Oct 2023 01:42

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Contributors

Author: Mitra Yousefi
Author: Wilfried Karmaus
Author: Hongmei Zhang
Author: Susan Ewart
Author: Hasan Arshad
Author: John W Holloway ORCID iD

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