[Show abstract][Hide abstract] ABSTRACT: PTX3 is a long pentraxin of the innate immune system produced by different cell types (mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells) at the inflammatory site. It appears to have a cardiovascular protective function by acting on the immune-inflammatory balance in the cardiovascular system. PTX3 plasma concentration is an independent predictor of mortality in patients with acute myocardial infarction (AMI) but the influence of PTX3 genetic variants on PTX3 plasma concentration has been investigated very little and there is no information on the association between PTX3 variations and AMI. Subjects of European origin (3245, 1751 AMI survivors and 1494 controls) were genotyped for three common PTX3 polymorphisms (SNPs) (rs2305619, rs3816527, rs1840680). Genotype and allele frequencies of the three SNPs and the haplotype frequencies were compared for the two groups. None of the genotypes, alleles or haplotypes were significantly associated with the risk of AMI. However, analysis adjusted for age and sex indicated that the three PTX3 SNPs and the corresponding haplotypes were significantly associated with different PTX3 plasma levels. There was also a significant association between PTX3 plasma concentrations and the risk of all-cause mortality at three years in AMI patients (OR 1.10, 95% CI: 1.01-1.20, p = 0.02). Our study showed that PTX3 plasma levels are influenced by three PTX3 polymorphisms. Genetically determined high PTX3 levels do not influence the risk of AMI, suggesting that the PTX3 concentration itself is unlikely to be even a modest causal factor for AMI. Analysis also confirmed that PTX3 is a prognostic marker after AMI.
[Show abstract][Hide abstract] ABSTRACT: We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin.
Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D.
Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12-1·37], P < 0·0001) and improved prognostic discrimination beyond clinical risk factors (integrated discrimination improvement, P = 0·005). Patients with increasing adiponectin concentration over 3 months had worse outcome than those with stable levels (unadjusted HR = 1·46[1·09-1·96], P = 0·01); this relation was attenuated by the genetic variants examined and by robust confounders like age, diabetes, BMI or NT-proBNP (adjusted HR = 1·37[0·97-1·94], P = 0·075).
Although diabetes and genetic variants at the ADIPOQ gene influence the circulating levels of adiponectin in CHF, higher plasma adipokine levels, but not genetic variants, are consistently associated with a poor prognosis.
No preview · Article · May 2011 · European Journal of Clinical Investigation
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD), a modest number considering the apparent heritability of CAD. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ∼575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
[Show abstract][Hide abstract] ABSTRACT: While many studies have shown an association between the gene coding for adiponectin (ADIPOQ) and adiponectin levels, much more controversy surrounds its association with metabolic traits such as insulin resistance, obesity and type 2 diabetes. Furthermore, very few studies have looked into the relations between ADIPOQ variants and risk of cardiovascular disease. The present study assessed the influence of four common ADIPOQ Single Nucleotide Polymorphisms (SNPs), rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T) on the risk of myocardial infarction and type 2 diabetes.
A large genetic association case-control study was conducted in 2008 Italians, including patients with myocardial infarction, type 2 diabetes, or both, and a reference group of healthy controls. Homozygotes TT for the rs1501299 (+276) had half the risk of either myocardial infarction alone or in association with type 2 diabetes when compared to the carriers of the G allele (OR = 0.58, p =0.01, and OR = 0.55, p =0.006 respectively). SNPs rs17300539 (-11391), rs266729 (-11377) and rs2241766 (+45) showed no significant association with any of the three case groups.
These results suggest that homozygotes TT for the adiponectin polymorphism rs1501299 (+276) are protected from the risk of myocardial infarction.
No preview · Article · Aug 2010 · Therapeutic Advances in Cardiovascular Disease
[Show abstract][Hide abstract] ABSTRACT: A genomic region on chromosome 9p21 has been identified as closely associated with increased susceptibility to coronary artery disease (CAD) and to type 2 diabetes (T2D) although the evidence suggests that the genetic variants within chromosome 9p21 that contribute to CAD are different from those that contribute to T2D.We carried out an association case-control study in an Italian population to test the association between two single nucleotide polymorphisms (SNPs) on the 9p21 locus, rs2891168 and rs10811661, previously reported by the PROCARDIS study, and respectively myocardial infarction (MI) and T2D. Our aim was to confirm the previous findings on a larger sample and to verify the independence of their susceptibility effects: rs2891168 associated with MI but not with T2D and rs10811661 associated with T2D but not with MI.
Genomic DNA samples of 2407 Italians with T2D (602 patients), who had had a recent MI (600), or had both diseases (600) and healthy controls (605) were genotyped for the two SNPs. The genotypes were determined by allelic discrimination using a fluorescent-based TaqMan assay.
SNP rs2891168 was associated with MI, but not with T2D and the G-allele odds ratio (OR) was 1.20 (95% CI 1.02-1.41); SNP rs10811661 was associated with T2D, but not with MI, and the T-allele OR was 1.27 (95% CI 1.04-1.55). ORs estimates from the present study and the PROCARDIS study were pooled and confirmed the previous findings, with greater precision.
Our replication study showed that rs2891168 and rs10811661 are independently associated respectively with MI and T2D in an Italian population. Pooling our results with those reported by the PROCARDIS group, we also obtained a significant result of association with diabetes for rs10811661 in the European population.
Full-text · Article · Apr 2010 · BMC Medical Genetics