[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.]

We studied the relationship between the leucocyte telomere length (LTL) and the copy number of mitochondrial DNA (CNmtDNA) and the development of acute coronary syndrome during 15 years of follow-up. A random population sample was examined at baseline in 2003-2005 (n=9 360, men and women 45-69 years old, Novosibirsk, the HAPIEE project) and followed-up for 15 years. In the frame of nested case-control design, we selected cases - incident myocardial infarction/acute coronary syndrome (MI/ACS) among those free from baseline CVD (n=256) and sex- and age-stratified control among those free from baseline CVD and cancer and alive by the end of follow-up (n=799). The relative LTL and CNmtDNA were assessed using quantitative real-time PCR. Results. The carriers of shorter telomeres had increased 15-year risk of MI/ACS with adjusted OR=1,87 (95% CI 1,70-2,06) per 1 LTL decile independent of other factors. Fewer CNmtDNA was associated with increased risk of MI/ACS with adjusted OR=1,19 (95% CI 1,12-1,26) per 1 CNmtDNA decile. The identified associations were confirmed in tertile analysis and in stepwise analysis with continuous variables of both biomarkers. All associations persisted after adjusting for gender, age, and traditional CVD risk factors. Conclusion. The LTL and CNmtDNA were independent predictors of the 15-year risk of MI/ACS in the middle- and elderly Siberian (Caucasoid) population cohort. These findings highlight the need for further research to elucidate the mechanisms by which LTL and mtDNA copy number may affect human health.

Verification of Single Nucleotide Polymorphisms rs34554140, rs6670279, and rs6874185 as Novel Molecular Genetic Markers of Sudden Cardiac Death.

The aim of the study was to explore the association between sudden cardiac death (SCD) and single nucleotide polymorphisms (SNPs) rs34554140, rs6670279, and rs6874185 from the list of potential molecular genetic markers of SCD, obtained in our earlier genome-wide allelotyping on pooled DNA samples. Materials and Methods: The study is based on the case-control principle. The SCD group included 438 deceased residents of Novosibirsk (average age - 53.2±9.1 years; men - 72.7%, women - 28.3%) with the main postmortem diagnoses of acute circulatory failure or acute coronary failure, which met the criteria of SCD established by the European Society of Cardiology. The control group included 435 live subjects enrolled in the international projects HAPIEE and MONICA (average age - 53.2±8.9 years; men - 70.0%, women - 30.0%). DNA was isolated by phenol-chloroform extraction from the myocardial tissue in the SCD group and from the venous blood in the control group. Genotyping was performed by polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism in a polyacrylamide gel. Results: The frequencies of the genotypes of SNPs rs34554140, rs6670279, and rs6874185 in the control group correspond to those predicted by the Hardy-Weinberg equilibrium (c2=0.98, 0.009, 3.39, respectively). The AA genotype of rs34554140 is associated with an increased risk of SCD (p=0.002; OR=1.85; 95% CI 1.26-2.71). The AT genotype has a protective effect against SCD (p=0.001; OR=0.53; 95% CI 0.36-0.78). In subgroups separated by gender and age, the differences persist in the subgroups of men, women, and individuals under 50 years old (p<0.05). The AA genotype of rs6670279 is associated with an increased risk of SCD (p=0.005; OR=1.54; 95% CI 1.15-2.06). The AT genotype has a protective effect against SCD (p=0.047; OR=0.73; 95% CI 0.54-0.98). When distributed by sex and age, the differences persist in the subgroups of men, individuals above 50 years old, and men above 50 years old (p<0.05). There were no significant differences in the frequencies of genotypes and alleles of rs6874185 between the SCD and control groups, even after the subgroups specified by gender and age were compared (p>0.05). Conclusion: The association of single nucleotide polymorphisms rs34554140 and rs6670279 with SCD was confirmed. In contrast, no association of rs6874185 with SCD was detected.