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.

作者: Susan Ewart , Hasan Arshad , John W Holloway , Hongmei Zhang , Mitra Yousefi

DOI:

关键词: Body regionDNA methylationCpG siteSingle-nucleotide polymorphismLeptinPregnancyBiologyLeptin receptorEndocrinologyOffspringInternal medicine

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

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