Division of Genomic Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, 363-951, Republic of Korea.
Sci Rep. 2019 Feb 12;9(1):1815. doi: 10.1038/s41598-019-38538-2.
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.
低密度脂蛋白受体相关蛋白 1B（LRP1B）与属于低密度脂蛋白受体家族的巨大脂蛋白受体相关蛋白 1 同源。先前对 LRP1B 基因的遗传关联研究表明，该基因与肥胖有关。通过对儿童重度肥胖队列（n=692）的 LRP1B 基因外显子组测序，我们在第 4 内含子中发现了一种新的单核苷酸多态性（rs431809），该多态性与体重指数（BMI）和腰臀比（WHR）显著相关。同一内含子中的 3 个 CpG 位点（cg141441481、cg01852095 和 cg141441470）的甲基化也与 BMI 和 WHR 显著相关。所有 CpG 甲基化均呈双峰模式，且依赖于 rs431809 基因型。肥胖对 LRP1B 基因的遗传影响可能与同一内含子中 CpG 甲基化的相互作用有关。SNP 的遗传影响与 LRP1B 中的表观遗传相互作用有关。LRP1B 基因的遗传和表观遗传相互作用可能与儿童肥胖的预防和治疗方法有关。
