title: Preliminary evidence for an association between LRP-1 genotype and body mass index in humans.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama, Birmingham, Alabama, United States of America. LekkiWood@Gmail.com
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C475476:LRP1 protein, human; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D014280:Triglycerides; C030087:lipoprotein triglyceride