A specific variant of the LRP1B gene, and other alterations that affect protein production from this gene, are associated with severe obesity in children, according to a new study.
The research, “The genetic and epigenetic association of LDL Receptor Related Protein 1B (LRP1B) gene with childhood obesity,” was published in the journal Nature Scientific Reports.
LRP1B gene variants have been identified as risk factors for obesity, being associated with increased body mass index (BMI) and insulin resistance. This gene has also been implicated in cancer, showing DNA and RNA alterations in cell lines of non-small cell lung cancer.
Epigenetic changes — changes in gene expression, rather than in the gene itself — in LRP1B alter the tumor environment in acute lymphoblastic leukemia and in gastric cancer, while in colon cancer the LRP1B protein blocks the growth and metastasis of tumor cells.
Now, a researcher from Korea’s National Institute of Health evaluated LRP1B variants in a group of 692 children to assess the effect of genetic changes in childhood obesity. The group included 305 children (159 males) with severe obesity — average age 13.94 years, average BMI 31.71 kg/m2 — and 387 controls (199 males).
Blood samples from the children were analyzed through exome sequencing, which refers to sequencing of the genetic sequence of all DNA bits in the LRP1B gene that contain information to generate proteins; these bits of coding DNA are called exons.
Results showed that a single nucleotide polymorphism (SNP) — a difference in a single nucleotide, the building blocks of DNA — known as rs431809 was associated with both BMI and waist-hip circumference ratio (WHR), a common measure of obesity. This variant was found in the gene’s intron 4. Introns are sequences that are removed in the formation of the final RNA product for protein production.
A subsequent analysis revealed that this SNP in LRP1B was significantly associated with childhood obesity. Having the least frequent genotype (found in 21 children) of this specific variant correlated with higher BMI and WHR, compared to the two other possible genotypes.
Furthermore, three methylations — epigenetic changes that consist in the addition of methyl chemical groups to the DNA molecule — in intron 4 also correlated with higher BMI and WHR. These alterations occurred at CpG sites, which are DNA spots where a guanine (G) nucleotide follows a cytosine (C) nucleotide.
Two of the three epigenetic alterations were associated with the specific rs431809 genotype found.
According to the team, the study is the first “to validate the association of rs431809 in childhood obesity related to CpG methylation.”
The team also suggested that “genetic and epigenetic interplay of LRP1B gene may be implicated in the prevention and therapeutic approach to childhood obesity.”