title: Association of rs1466535 LRP1 but not rs3019885 SLC30A8 and rs6674171 TDRD10 gene polymorphisms with abdominal aortic aneurysm in Italian patients.
abstract: OBJECTIVE
  Recently, a large genome-wide association study in patients with abdominal aortic aneurysm (AAA) and control subjects identified nine loci associated with AAA. Besides the significant association of the rs1466535 single nucleotide polymorphism in the low-density lipoprotein receptor-related protein 1 gene (LRP1), two of eight remaining loci, rs6674171 in the tudor domain containing protein 10 (TDRD10) and rs3019885 in solute carrier family 30 zinc transporter member 8 (SLC30A8) gene, showed a weakly significant association with AAA requiring further attention. Therefore, the aim of our study was to evaluate the role of these three polymorphisms in conferring AAA genetic susceptibility.
  
  
  METHODS
  We studied these three polymorphisms in 423 patients and 423 sex- and age-comparable control subjects from Italy. All subjects were genotyped with the use of the real-time TaqMan approach. Multiple logistic regression analysis adjusted for traditional cardiovascular risk factor and chronic obstructive pulmonary disease was used to estimated odds ratios and 95% confidence intervals for AAA risk.
  
  
  RESULTS
  The prevalence of carriers of the rs3019885 SLC30A8 G allele was higher in control subjects (67.8%) than in patients (60.3%, P = .022), suggesting a protective effect for AAA. The prevalence of carriers of the rs1466535 LRP1 T allele was higher in patients (51.8%) than in control subjects (39.7%, P = .0004), suggesting a risk effect for AAA. rs6674171 polymorphism genotype distribution did not differ between AAA patients and control subjects. In the multiple logistic regression analysis adjusted for traditional AAA risk factors, only the rs1466535 polymorphism remained significantly associated with AAA (odds ratio, 1.85; 95% confidence interval, 1.2-2.84; P = .01).
  
  
  CONCLUSIONS
  Our findings confirm the role as significant and independent susceptibility factor for AAA of the rs1466535 LRP1 polymorphism (T allele) in an Italian population. Nevertheless, our findings consistently differed from previous published data because in the genome-wide association study, the risk allele was the most frequent rs1466535 C allele. Our findings are consistent with literature data of LRP1 knock-out mice developing atherosclerotic lesions and aortic dilatation and association of the T allele with reduced LRP1 gene expression in humans.
  
  
  CONCLUSIONS
  Our work supports the evidence that the T allele of the rs1466535 LRP1 polymorphism is an independent risk factor for abdominal aortic aneurysm. Our findings are consistent with literature data of Lrp1 knock-out mice developing atherosclerotic lesions and aortic dilatation, and association of the T allele with reduced LRP1 gene expression in humans. These data could have a crucial role for developing future diagnostic or prognostic scores based on biohumoral, clinical, genetic, proteomic, and imaging data to be applied in everyday clinical practice in order to improve the management of these high-risk patients in consideration of their characteristics and pathophysiological complexity.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galora
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Saracini
authors.affiliation: Department of Biomedicine and Prevention, Unit of Vascular Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pratesi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Vascular Surgery Unit, Careggi Hospital, Florence, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pulli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Vascular Surgery Unit, Careggi Hospital, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pratesi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Vascular Surgery Unit, Careggi Hospital, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Vascular Surgery Unit, Careggi Hospital, Florence, Italy. Electronic address: betti.giusti@unifi.it.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D016601:RNA-Binding Proteins; C492522:SLC30A8 protein, human; C000597199:TDRD10 protein, human; D000075703:Zinc Transporter 8