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Background/Aims  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 ε3/ε3 genotype against mutant  ApoE  allele (ε2/ε4) carriers.    Methods/Results  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 ε2 or ε4 allele carriers ( P >0.05).    Conclusions  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.

Preliminary Evidence for an Association between LRP-1 Genotype and Body Mass Index in Humans