Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer’s Disease Patients

Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44±6.28 vs. 76.36±6.39, p=0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61±5.88 vs. 78.57±6.79, p=0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients

Cardiac autonomic dysfunction in adult congenital heart disease

Abstract Purpose Due to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD. Methods Ninety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring. Results As compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001). After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest. Conclusion ACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD