title: Low-density lipoprotein receptor-related protein 1 variant interacts with saturated fatty acids in Puerto Ricans.
abstract: OBJECTIVE
  Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not been evaluated for obesity in people.
  
  
  METHODS
  We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area.We examined whether dietary fats (eg., saturated, polyunsaturated) modulated the association of LRP1 rs1799986 with anthropometric traits. We studied a population-based sample of Puerto Ricans (n = 920, aged 45-74 y) living in the Boston area.
  
  
  RESULTS
  In multivariable linear regression models, we dichotomized saturated fat intake and found significant interaction terms between total saturated fatty acids and LRP1 rs1799986 genotype for BMI (P=0.006) and hip (P = 0.002). High intake of saturated fat was associated with higher BMI (P = 0.001), waist (P = 0.008) and hip (P=0.003) in minor allele carriers (CT+TT) compared to CC participants. Further analysis of dichotomized individual saturated fatty acids revealed that interactions were strongest for two individual longer chain fatty acids. High intake of palmitic acid (C16:0; P = 0.0007) and high stearic acid intake (C18:0; P = 0.005) were associated with higher BMI in T carriers. Interactions were not detected for polyunsaturated fatty acids.
  
  
  CONCLUSIONS
  Gene-diet interactions at the LRP1 locus support the hypothesis that susceptibility to weight gain based on saturated fatty acids is modified by genotype and possibly by chain length. These results may facilitate the development of a panel of genetic candidates for use in optimizing dietary recommendations for obesity management.
authors: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.
authors: Caren E
authors: CE
authors: Smith
authors: Katherine L
authors: KL
authors: Tucker
authors: Yu-Chi
authors: YC
authors: Lee
authors: Chao-Qiang
authors: CQ
authors: Lai
authors: Laurence D
authors: LD
authors: Parnell
authors: José M
authors: JM
authors: Ordovás
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000368:Aged; D015992:Body Mass Index; D001900:Boston / Q000453:epidemiology; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D005227:Fatty Acids / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics* / Q000706:statistics & numerical data; D006801:Humans; D020738:Leptin / Q000097:blood; D008019:Life Style; D016014:Linear Models; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015596:Nutrition Assessment; D009765:Obesity / Q000208:ethnology* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011647:Puerto Rico / Q000208:ethnology; D011795:Surveys and Questionnaires
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; C475476:LRP1 protein, human; D020738:Leptin; D026503:Low Density Lipoprotein Receptor-Related Protein-1
references: Eur J Clin Nutr. 1998 Jan;52(1):2-6
references: 9481524
references: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4661-6
references: 15070774
references: J Nutr. 1991 Jan;121(1):31-6
references: 1992055
references: J Neurosci. 2009 Jan 14;29(2):359-70
references: 19144836
references: J Biol Chem. 2009 Jan 2;284(1):381-388
references: 18990694
references: PLoS Biol. 2011 Jan 11;9(1):e1000575
references: 21264353
references: Lancet. 2003 Feb 15;361(9357):598-604
references: 12598158
references: PLoS One. 2012;7(2):e30732
references: 22347399
references: PLoS One. 2009 Oct 12;4(10):e7422
references: 19823686
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Asia Pac J Clin Nutr. 2003;12(2):151-60
references: 12810404
references: Physiol Behav. 2010 Aug 4;101(1):161-7
references: 20451538
references: J Biol Chem. 2011 May 13;286(19):16775-82
references: 21454706
references: J Nutr. 2003 Nov;133(11):3651-7
references: 14608089
references: J Nutr. 2009 Nov;139(11):2011-7
references: 19776189
references: PLoS Genet. 2006 May;2(5):e81
references: 16733553
references: Nucleic Acids Res. 2002 Jan 1;30(1):207-10
references: 11752295
references: Nat Genet. 2010 Nov;42(11):937-48
references: 20935630
references: BMC Public Health. 2010 Mar 01;10:107
references: 20193082
references: Am J Epidemiol. 1998 Sep 1;148(5):507-18
references: 9737563
references: Int J Obes Relat Metab Disord. 2003 Jan;27(1):95-102
references: 12532160
references: Int J Obes (Lond). 2011 Feb;35(2):251-8
references: 20603626
references: Int J Food Sci Nutr. 2010 May;61(3):282-94
references: 20095912
references: Cell. 2008 Oct 3;135(1):61-73
references: 18854155
references: Physiol Genomics. 2005 May 11;21(3):351-61
references: 15888570
references: N Engl J Med. 2009 Feb 26;360(9):859-73
references: 19246357
references: Physiol Rev. 2008 Jul;88(3):887-918
references: 18626063
references: Nat Genet. 1996 Sep;14(1):95-7
references: 8782827
references: Nutrition. 2006 Jan;22(1):60-8
references: 16226011
references: Nutr Rev. 2010 Apr;68(4):214-31
references: 20416018
references: J Biol Chem. 2003 Apr 4;278(14):11945-53
references: 12551936
references: Eur J Endocrinol. 1998 Aug;139(2):224-30
references: 9724081
references: Am J Clin Nutr. 2008 Mar;87(3):621-6
references: 18326600
references: J Atheroscler Thromb. 2003;10(5):290-8
references: 14718746
references: Nat Genet. 2004 May;36(5):512-7
references: 15052271
references: Br J Nutr. 2010 Jun;103(12):1702-5
references: 20100377
references: Nat Genet. 2009 Jan;41(1):18-24
references: 19079260
references: J Clin Invest. 2007 Nov;117(11):3271-82
references: 17948131
references: Metabolism. 2007 Jul;56(7):985-91
references: 17570262