title: Low-density lipoprotein receptor-related protein 5 gene polymorphisms and genetic susceptibility to abdominal aortic aneurysm.
abstract: BACKGROUND
  Previous data showed decreased low-density lipoprotein receptor-related protein 5 (LRP5) gene expression in peripheral blood cells of abdominal aortic aneurysm (AAA) patients and an association between decreased expression of LRP5 and increased lipoprotein (a) [Lp(a)] levels in AAA. LRP5 gene is involved in bone, lipid, and glucose metabolism, and experimental studies showed that atherosclerotic lesions of ApoE:LRP5 double knockout mice were ~threefold greater than those in ApoE-knockout mice and were characterized by features of advanced atherosclerosis, with remarkable accumulation of foam cells and destruction of the internal elastic lamina. The aim of this study was to evaluate the role of polymorphisms in LRP5 gene in determining genetic susceptibility to AAA.
  
  
  METHODS
  A total of 423 AAA patients and 423 controls comparable for sex and age were genotyped for seven polymorphisms within the LRP5 (rs667126, rs3736228, rs4988300, rs3781590, rs312016, rs556442, rs627174) by TaqMan approach.
  
  
  RESULTS
  Two polymorphisms were significantly associated with AAA: rs4988300, carriers of the T allele in AAA (74.0% vs 65.3% in controls; P = .007); and rs3781590, carriers of the T allele in AAA (66.5% vs 57.4% in controls; P =.009). At the multiple logistic regression analysis, adjusted for age, sex, dyslipidemia, hypertension, smoking habit, and chronic obstructive pulmonary disease, rs4988300 and rs3781590 polymorphisms remained significant and independent determinants of AAA (OR, 1.62; 95% CI, 1.02-2.56; P = .040, and OR, 1.83; 95% CI, 1.17-2.85; P = .008, respectively). We confirmed that AAA patients had significantly higher Lp(a) levels than control subjects (180.0 mg/L vs 107.6 mg/L; P < .0001). The prevalence of patients with Lp(a) levels ≥ 300 mg/L was significantly higher in patient carriers of the rs4988300 T allele than in wild-type patients (42.6% vs 30.8%; P = .048).
  
  
  CONCLUSIONS
  Present data have identified rs4988300 and rs3781590 LPR5 polymorphisms as independent genetic markers of AAA and underlined the need to concentrate our effort in studying the role of these markers in AAA and of LRP5 gene in Lp(a) catabolism and AAA pathophysiology.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Atherothrombotic Diseases Center AOU Careggi, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galora
authors.forename: Claudia
authors.initials: C
authors.lastname: Saracini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Palombella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pratesi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pulli
authors.forename: Carlo
authors.initials: C
authors.lastname: Pratesi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D017270:Lipoprotein(a) / Q000097:blood; D016015:Logistic Models; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C555482:LRP5 protein, human; D017270:Lipoprotein(a); D060492:Low Density Lipoprotein Receptor-Related Protein-5