title: LRP1 gene polymorphisms are associated with premature risk of cardiovascular disease in patients with familial hypercholesterolemia.
abstract: OBJECTIVE
  LRP1 gene overexpression in atherosclerotic plaque is associated with increased lipid uptake through the vascular wall. The aim of the study was to analyze whether LRP1 modulates the genetic risk of developing premature cardiovascular disease in familial hypercholesterolemia, using single nucleotide polymorphism association analysis.
  
  
  METHODS
  Ten polymorphisms of the LRP1 gene (rs715948, rs1799986, rs1800127, rs7968719, rs1800176, rs1800194, rs1800181, rs1140648, rs1800164, and rs35282763) were genotyped in 339 patients (77 with premature cardiovascular disease and 262 without) in the SAFEHEART study.
  
  
  RESULTS
  The c.677C>T (rs1799986) polymorphism showed a significant association with premature cardiovascular disease after adjusting by sex, age, body mass index, and the effect of the low-density lipoprotein receptor mutation in the dominant model (CT+TT vs CC: odds ratio=1.94; 95% confidence interval, 1.08-3.48; P=.029). Similar results were observed after increasing the sample to 648 subjects (133 with premature cardiovascular disease vs 515 without [odds ratio=1.83; 95% confidence interval, 1.16-2.88; P=.011]).
  
  
  CONCLUSIONS
  The c.677C>T polymorphism is associated with increased rates of premature cardiovascular disease in familial hypercholesterolemia. Although we were unable to show that this polymorphism was involved in the alteration of normal mRNA splicing patterns, the possibility that it is in strong linkage disequilibrium with another functional polymorphism cannot be ruled out and would explain the cause-effect relationship with cardiovascular disease risk in this population. Further studies are needed to replicate the results and to localize the putative genetic variants associated with this polymorphism.
authors: Centro de Investigación Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors: Rosa
authors: R
authors: Aledo
authors: Rodrigo
authors: R
authors: Alonso
authors: Pedro
authors: P
authors: Mata
authors: Vicenta
authors: V
authors: Llorente-Cortés
authors: Teresa
authors: T
authors: Padró
authors: Lina
authors: L
authors: Badimon
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1