Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study.

BACKGROUND: The influence of biomarkers in human lifespan has been investigated but with no clear results yet. MATERIALS AND METHODS: Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2). RESULTS: Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively). CONCLUSION: Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family's lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

The Association between TGF-ß1 G915C (Arg25Pro) Polymorphism and the Development of Primary Open Angle Glaucoma: A Case-Control Study.

The purpose of the current study was to identify the potential association between Single Nucleotide Polymorphism (SNP) TGFß1 +915 (C or G) in codon 25 and Primary Open Angle Glaucoma (POAG). Overall, 88 cases with POAG and a control group of 52 healthy individuals were recruited from the First Ophthalmology Department of Athens University. DNA was isolated from whole blood samples and genotype frequencies for the polymorphism rs1800471 (G915C, Arg25Pro) of the TGF-ß1 gene were assessed. Genotype distribution frequencies for the polymorphism rs1800471 (G915C, Arg25Pro) of the TGF-ß1 gene were not statistically different between patients with POAG and control subjects. The present study failed to determine any significant genotypic association with POAG, despite the fact that the presence of the C allele was scarcely increased in the POAG when compared with the control group.

Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy.

BACKGROUND: Hypertension, one of the most important risk factors for premature cardiovascular disease, is a major worldwide public health problem. Angiotensin-1-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these gene polymorphisms in an adult population with and without essential hypertension. Furthermore, we evaluated the effect of ACE and AGT gene polymorphisms on ramipril treatment efficacy in the hypertensive patients. METHODS: A total of 166 adults (83 hypertensives and 83 normotensives) were involved in the study and genotyped for AGTM235T (rs699), AGTT174M (rs4762) and ACEI/D (rs1799752) gene polymorphisms. RESULTS: The genotype and allele distribution of the AGTM235T variant significantly differed between hypertensives and normotensives [odds ratio (OR) = 1.57% (T vs M allele), 95% confidence intervals (CIs): 1.01 - 2.44; p=0.045 for hypertensives]. However, none of the 3 studied Simple Nucleotide Polymorphisms were associated with the blood pressure-lowering response to ramipril. CONCLUSION: These results suggest that AGTM235T gene polymorphism is associated with essential hypertension. However, none of the AGTM235T, AGTT174M and ACEI/D gene polymorphisms influenced ramipril effectiveness.

Heart-type fatty acid binding protein in elective cardioversion of atrial fibrillation.

OBJECTIVES: We sought to investigate whether heart-type fatty acid binding protein (H-FABP), a new marker of myocardial necrosis, increases in relation to elective cardioversion of atrial fibrillation (AF). METHODS: We studied 25 consecutive patients (61 ± 16 years old, 21 men) admitted to our hospital for elective cardioversion of AF. Peripheral venous samples were drawn immediately before cardioversion, one hour and 24h after the procedure and assayed for H-FABP. RESULTS: A mean of 309 ± 183 J was used for cardioversion. Successful cardioversion in sinus rhythm was achieved in 18 patients (72%). Serum levels of H-FABP did not change significantly either in relation to the procedure [1385 (256-17,127)pg/mL at baseline, 1125 (290-15,238)pg/mL 1h post and 1045.5 (66-2981)pg/mL 24 h post cardioversion, p=0.37] or to the success of the procedure. CONCLUSION: H-FABP does not significantly change following elective cardioversion for AF and we, therefore, speculate that myocardial necrosis does not occur during cardioversion.

Association of apolipoprotein E genotype with early onset of coronary heart disease in Greek men.

Apolipoprotein (apo) E polymorphism has been associated with coronary heart disease (CHD) although its relation to the age of CHD onset is still not defined. The age of onset of established CHD was obtained from 502 Greek men and compared to 103 healthy men. The age grouping was based on the age of CHD onset (earlier < or =44 years, n = 73, intermediate 45-64 years, n = 321, and later > or =65 years, n = 108). Apo E genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the lipid profile was assessed. No differences in genotype and allele frequencies were found within the CHD groups. The apo epsilon3/4 genotype and the apo epsilon4 allele were less frequent in the earlier-onset group than in healthy men (11.0 % vs 22.3%, Pearson Chi-Square p = 0.028 and 6.8% vs 13.6%, Pearson Chi-Square p = 0.023, respectively). The lipid profile was similar in all genotypes of all groups except for high-density lipoprotein cholesterol levels, which were higher in epsilon2 carriers compared to non-epsilon2 carriers (in mg/dL [+/-SD]; 44 [9] vs 39 [10], in mmol/L [+/-SD]; 1.1 [0.2] vs 1.0 [0.3] p = 0.005). There is an association between apo E genotype and early onset of CHD in Greek men. In the earlier CHD onset group, the apo epsilon3/4 genotype was less frequent compared to healthy men. This supports that the apo epsilon3/4 genotype is associated with decreased risk of premature CHD. Because the results of similar studies are not consistent, it may be that the relationship between apo E genotype and CHD is related to ethnicity rather than a universal phenomenon.