title: Genetic score based on high-risk genetic polymorphisms and early onset of ischemic heart disease in an Italian cohort of ischemic patients.
abstract: Several single-nucleotide polymorphisms (SNPs) have been recognized as associated with ischemic heart disease (IHD) although the optimal set of risk genotypes has not be identified. This study aimed to examine whether identified high-risk SNPs are associated with early onset of IHD. In the GENOCOR study, 44 high-risk SNPs were genotyped in 114 patients with early onset of IHD (46.2 ± 5.1 years) and 384 patients with late onset of IHD (60.7 ± 5.9 years). The associations between individual SNPs and early onset IHD were assessed. A multilocus genetic risk score (GRS) for each associated risk genetic markers was constructed by summing the number of risk alleles. The SNPs significantly associated with IHD were: -482C>T of Apolipoprotein C III gene (ApoC3, p=0.02); 1171 5A>6A of Matrix metalloproteinase 3 stromelisine I gene (p=0.01); G98T of Selectin E gene (p=0.05); C/G of 9p21.3 locus (p=0.01). Likelihood ratio test showed a strong interaction for increasing risk of early IHD between the presence of ApoC3 and 9p21.3 locus with hypertriglyceridemia (p=0.0008, 0.0011) as well as between 9p21.3 locus and smoking (p=0.0010) after correction for multiple testing. The OR for premature IHD for GRS unit was 1.3 (95% CI 1.1-1.6, p=0.001). Patients in the top tertile of GRS were estimated to have a 3.2-fold (95% CI 1.5-6.8; p=0.001) increased risk of early IHD compared with those in the bottom tertile. The results show that currently identified high-risk SNPs confer an additive biomarker for cardiovascular events. GRS may provide important incremental information on the genetic component of IHD.
authors.affiliation: Istituto di Fisiologia Clinica-CNR, Pisa, Italy. Electronic address: vecoli@ifc.cnr.it.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.affiliation: Atlas, Trowbridge BA14 0XG, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Adlerstein
authors.affiliation: Euroclone Diagnostica Srl, Siziano (PV), Italy.
authors.forename: Erlet
authors.initials: E
authors.lastname: Shehi
authors.affiliation: Fondazione CNR-Regione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Bigazzi
authors.affiliation: Fondazione CNR-Regione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Sampietro
authors.affiliation: Istituto di Fisiologia Clinica-CNR, Pisa, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.affiliation: Istituto di Fisiologia Clinica-CNR, Pisa, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Carpeggiani
authors.affiliation: Istituto di Fisiologia Clinica-CNR, Pisa, Italy; Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: L'abbate
authors.affiliation: Istituto di Fisiologia Clinica-CNR, Pisa, Italy; Fondazione CNR-Regione Toscana Gabriele Monasterio, Pisa, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
keywords: early IHD; genetic risk score; high-risk polymorphisms