Abstract
Low-density lipoprotein Receptor Related Protein 1B (LRP1B) is homologous to the gigantic lipoprotein receptor-related protein 1 that belongs to the family of Low-density lipoprotein receptors. Previous genetic association studies of the LRP1B gene have shown its genetic association with obesity. Through exome sequencing of the LRP1B gene from a childhood severe obesity cohort (n = 692), we found novel single nucleotide polymorphism (rs431809) in intron 4, which has been significantly correlated with both body mass index (BMI) and waist-hip-ratio (WHR). Three methylations of CpG sites (cg141441481, cg01852095 and cg141441470) in the same intron were also significantly correlated with BMI and WHR. All CpG methylations had bimodal patterns, and were dependent on rs431809 genotypes. The genetic influences of obesity on the LRP1B gene may be linked to the interplay of CpG methylations in the same intron. Heritability of SNP interacts with epigenetic crosstalk in LRP1B. Genetic and epigenetic crosstalk of LRP1B gene may be implicated in the prevention and therapeutic approach to childhood obesity.
Highlights
Low-density lipoprotein Receptor Related Protein 1B (LRP1B) is highly homologous to the gigantic lipoprotein receptor-related protein 1 that belongs to the family of low-density lipoprotein receptors (LRP)[1]
We found an intronic single nucleotide polymorphism (SNP) which was associated with Body Mass Index (BMI) and waist-hip-ratio
Before frequency and genotyping pruning, exome sequencing showed 235 single nucleotide variants existed at LRP1B
Summary
Low-density lipoprotein Receptor Related Protein 1B (LRP1B) is highly homologous to the gigantic lipoprotein receptor-related protein 1 that belongs to the family of low-density lipoprotein receptors (LRP)[1]. We performed the genetic and epigenetic association study of LRP1B gene with obesity-related traits, as well as the sequence dependent methylation patterns linked to childhood obesity. Statistical analysis for DNA methylation study was performed by non-parametric methods because of bimodal data distribution. We performed exome sequencing of LRPB1 gene from 692 blood samples to find any genotype which associated with BMI and WHR.
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