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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, OBESITY, CARDIOVASCULAR HEALTH AND GENOMICS Title: Preliminary evidence for an association between LRP-1 genotype and body mass index in humans

Authors
item Frazier-Wood, Alexis -
item Kabagambe, Edmond -
item Borecki, Ingrid -
item Tiwari, Hemant -
item Ordovas, Jose -
item Arnett, Donna -

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 26, 2011
Publication Date: February 8, 2012
Citation: Frazier-Wood, A.C., Kabagambe, E.K., Borecki, I.B., Tiwari, H.K., Ordovas, J.M., Arnett, D.K. 2012. Preliminary evidence for an association between LRP-1 genotype and body mass index in humans. PLoS One. 7(2):e30732.

Interpretive Summary: Low density lipoprotein receptor-related protein 1 (LRP1) is a protein forming receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene. The LRP-1 has been associated with obesity in animal models and this increase in fat mass may be mediated through a mechanism involving the clearance of plasma triglyceride-rich lipoproteins (TGRL), where the LRP interacts with apolipoprotein E (ApoE) on chylomicron remnants. Therefore, we examined whether there was an association between 3 single nucleotide polymorphisms (SNPs) on LRP-1, with body mass index (BMI), and whether any association between LRP-1 SNPs and BMI could be modified by polymorphisms on the APOE gene. For this purpose we used data from 1,036 men and women participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Our data show that individuals who were homozygous for the minor allele at the LRP-1 I10701 SNP had BMIs 1.03 kg/m(2) higher than major allele carriers. We did not find interaction between the LRP-1 I70701 genotype and the ApoE gene. This may pave the way for future research into individualized dietary interventions.

Technical Abstract: The LDL receptor-related protein-1 gene (LRP-1) has been associated with obesity in animal models, but no such association has yet been reported in humans. As data suggest this increase in fat mass may be mediated through a mechanism involving the clearance of plasma triglyceride-rich lipoproteins (TGRL), where the LRP interacts with apolipoprotein E (ApoE) on chylomicron remnants, we aimed to examine (1) whether there was an association between 3 single nucleotide polymorphisms (SNPs) on LRP-1 with body mass index (BMI) and (2) whether any association between LRP-1 SNPs and BMI could be modified by polymorphisms on the ApoE gene when comparing the wild type Epsilon 3/Epsilon 3 genotype against mutant ApoE allele (Epsilon 2/Epsilon 4) carriers. We used data from 1,036 men and women (mean age +/- SD = 49 +/- 16 y) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Mixed linear models, which controlled for age, sex, alcohol intake and smoking, as well as family pedigree and center of data collection, were calculated. Models that used LRP-1 genotype as a predictor of BMI revealed that individuals who were homozygous for the minor allele at the LRP-1 I10701 locus had BMIs, on average, 1.03 kg/m(2) higher than major allele carriers (P = 0.03). In subsequent mixed linear models that included main effects of LRP-1 I10701 SNP and ApoE alleles, and an interaction term the two genotypes, there was no interaction detected between the LRP-1 I70701 genotype with either the ApoE Epsilon 2 or Epsilon 4 allele carriers (P greater than 0.05). This has implications for starting to understand pathways from genotype to human BMI, which may operate through TGRL uptake at the LRP-1 receptor. This may pave the way for future research into individualized dietary interventions.

Last Modified: 10/22/2014
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