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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., Clinical Relevance: 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., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: An association between rs1466535 low density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and abdominal aortic aneurysm (AAA) was recently demonstrated. It has not yet been defined if this association is specific for AAA or related to atherosclerosis per se. Therefore, we aimed to evaluate the role of the rs1466535 polymorphism in conferring genetic susceptibility for carotid artery stenosis (CAS)., Methods: The rs1466535 polymorphism was evaluated in n = 814 patients with CAS and n = 814 subjects without evidence of carotid atherosclerosis by TaqMan technology., Results: The percentage of T allele rs1466535 carriers was significantly higher in CAS patients (49.3%) than in controls (43.9%, p = 0.032). At the multiple logistic regression analysis, the allele T carrier status did not remain a significant determinant of CAS., Conclusions: The rs1466535 LRP1 polymorphism is not a significant and independent risk factor for CAS. Our result suggests this polymorphism in the LRP1 gene is not associated with atherosclerosis in general as it is not associated with CAS (this study), whereas it is strictly associated with AAA (our previous paper)., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aims: CYP2C19 variant alleles are independent predictors of clopidogrel response variability and occurrence of major adverse cardiovascular events in high-risk vascular patients on clopidogrel therapy. Increasing evidence suggests a combination of platelet function testing with CYP2C19 genetic testing may be more effective in identifying high-risk individuals for alternative antiplatelet therapeutic strategies. A crucial point in evaluating the use of these polymorphisms in clinical practice, besides test accuracy, is the cost of the genetic test and rapid availability of the results. One hundred acute coronary syndrome patients were genotyped for CYP2C19*2,*3,*4,*5, and *17 polymorphisms with two platforms: Verigene(®) and the TaqMan(®) system., Results: Genotyping results obtained by the classical TaqMan approach and the rapid Verigene approach showed a 100% concordance for all the five polymorphisms investigated. The Verigene system had shorter turnaround time with respect to TaqMan. The cost of reagents for TaqMan genotyping was lower than that for the Verigene system, but the effective manual staff involvement and the relative cost resulted in higher cost for TaqMan than for Verigene., Conclusions: The Verigene system demonstrated good performance in terms of turnaround time and cost for the evaluation of the clopidogrel poor metabolizer status, giving genetic information in suitable time (206 min) for a therapeutic strategy decision.