title: Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.
abstract: In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence-Atherothrombotic Disease 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-Atherothrombotic Disease Center, Careggi Hospital, Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Magi
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev, Herlev, Denmark.
authors.forename: Pia R
authors.initials: PR
authors.lastname: Kamstrup
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence-Atherothrombotic Disease Center, Careggi Hospital, Florence, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence-SOD Patologia Medica, Center for Autoimmune Systemic Diseases, Behçet Center and Lupus Clinic, Careggi Hospital, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Martinelli
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center-Ospedale Maggiore Policlinico, Milan, Italy.|Scientific Direction, Fondazione Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence-Atherothrombotic Disease Center, Careggi Hospital, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence-Atherothrombotic Disease Center, Careggi Hospital, Florence, Italy.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017270:Lipoprotein(a) / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054556:Venous Thromboembolism / Q000235:genetics*; D055815:Young Adult
chemical_list: D017270:Lipoprotein(a)