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Background: There is accumulating evidence from the epidemiological field of telomere biology that telomere length plays an important role in the pathophysiology of cardiovascular disease. The RNA-dependent DNA polymerase, telomerase, is essential in regulating telomere length by acting as a reverse transcriptase. However, the relationship between telomerase activity and telomere length in cardiovascular disease is unclear. This is due, in part, to the paucity of information on the utility of a quantitative and routine assay for the determination of telomerase activity in circulating blood leukocytes. Methods: We used a validated, high-sensitive real-time quantitative telomeric repeat amplification protocol (RQ-TRAP) to determine telomerase activity in circulating blood leukocytes. Results: The present investigation demonstrated direct and reliable detection of telomerase activity of circulating blood leukocytes. Conclusion: The present investigation suggests the feasibility of using RQ-TRAP assay in routine screening of telomerase activity in blood specimens typically collected in a clinical/epidemiological setting. Clin Chem Lab Med 2009;47:870–3. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic–epidemiological data are available. Methods: Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs). Results: Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR=0.455, 95% CI=0.215–0.960, uncorrected p =0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation. Conclusion: In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders. [Copyright &y& Elsevier]

Abstract: Recent data have implicated a haplotype of the purinergic receptor P2Y, G-protein coupled, 12 gene (P2RY12), as potential risk determinant for atherothrombosis. However, to date, no prospective, genetic-epidemiological data are available. Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we examined the possible association of P2RY12 genetic variants, in particular a haplotype H2 (constituted by dbSNP rs10935838, rs2046934, rs5853517, and rs6809699) amongst 708 white males who subsequently developed a thromboembolic event (incident myocardial infarction (MI), ischemic stroke, or deep venous thromboembolism/pulmonary embolism (DVT/PE)) and amongst an equal number of age- and smoking-matched white males who remained free of reported vascular disease during follow-up (controls). The P2RY12 gene variants tested were in linkage disequilibrium. The haplotype H2 distribution was significantly different between the DVT/PE cases (12%) and their matched controls (21%), p-permuted=0.02. In an adjusted conditional logistic regression analysis, the haplotype H2 was significantly associated with a lower risk of incident DVT/PE as compared to the reference haplotype H1 (odds ratio=0.50, 95% CI=0.27–0.93, p =0.028). However, we found no evidence for an association of the P2RY12 variants or the haplotype H2 with incident MI or ischemic stroke. The present investigation provides evidence for an association of the P2RY12 haplotype H2 with lower risk of DVT/PE; however these findings require replication in other well-designed studies. [Copyright &y& Elsevier]

Abstract: Objective: Uncoupling protein 2, mitochondrial, (UCP2) gene variation has recently been implicated in type 2 diabetes mellitus (T2DM). To date, no prospective epidemiological data are available. Methods: The association between 14 UCP (UCP2–UCP3) gene cluster tagging-SNPs and incident T2DM was investigated in 22,715 Caucasian participants of the prospective Women''s Genome Health Study. All were free of known cardiovascular disease and diabetes at baseline. During a 13-year follow-up period, 1445 participants developed an incident T2DM. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2DM risk assuming an additive model. Stratified analysis by smoking status, and haplotype analysis were also performed. Results: No evidence for an association of any of the tagging-SNPs tested with T2DM risk. Further investigation using stratified analysis, and haplotype-based approach showed similar null findings. Conclusion: The present investigation suggests that the UCP gene cluster variation may not be useful predictor for T2DM risk assessment. [Copyright &y& Elsevier]

Abstract: Background: Recent studies have shown telomere-length shortening as a risk predictor for cardiovascular disease. However, to date, no prospective data are available on its potential involvement in venous thromboembolism (VTE). Methods: Using leukocyte DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we examined the relationship of mean telomere repeat copy number to single gene copy number (T/S ratio), using a modified quantitative polymerase chain reaction protocol, amongst 108 White males who subsequently developed a first ever VTE event and amongst an equal number of age- and smoking-matched White males who remained free of vascular events during follow-up (controls). Results: An inverse correlation between T/S ratios and age was observed in our controls (p =0.04). However, the T/S ratios were similar between cases and controls (p =0.31). Furthermore, in a multi-variable adjusted analysis, we found no evidence for an association of the observed T/S ratios with VTE risk (odds ratio=1.20; 95%CI=0.58–2.52; p =0.62). Conclusions: The present investigation found no evidence for an association of relative telomere length with risk of incident VTE. [Copyright &y& Elsevier]

Abstract: We sought to investigate whether genetic variability within the CRP gene affects CRP levels. C-reactive protein (CRP), an acute-phase reactant in inflammation, is an important predictor for cardiovascular disease. The genetic determinants of plasma CRP level remain unknown. We assessed the genotypes of two common polymorphisms within the CRP gene, an exonic 1059G > C and an intronic T > A base substitution, among 2397 participants of a community-based study; 1334 had no prior cardiovascular history, while 1063 had a prior cardiovascular history. Univariable and multivariable-adjusted analyses were performed to examine the association of CRP polymorphisms with CRP levels, modeling different modes of inheritance. The genetic polymorphisms were significantly associated with baseline CRP levels in univariable analysis (1059G > C: GG versus GC or CC genotypes, median CRP levels 0.22 versus 0.15mg/L, P < 0.0001; intronic T > A: TT versus AT versus AA genotypes, median CRP levels 0.19 versus 0.23 versus 0.24mg/L, P = 0.003). This relationship persisted after adjusting for age, sex, body mass index, ethnicity, hypertension, smoking, diabetes, hyperlipidemia, and aspirin use. Furthermore, these effects were present in subgroup analyses limited to those with and without prevalent coronary disease, and when assessed within Caucasians only. The present data provide evidence of a genetic component of CRP levels, independently of traditional risk factors for cardiovascular disease. Whether genetic markers can add to information yielded by high sensitivity CRP (hsCRP) in assessing cardiovascular risk needs further evaluation. [Copyright &y& Elsevier]