HIV-Infected Patients as a Model of Aging.

We appraised the relationship between the biological and the chronological age and estimated the rate of biological aging in HIV-infected patients. Two independent biomarkers, the relative telomere length and iron metabolism parameters, were analyzed in younger (<35) and older (>50) HIV-infected and uninfected patients (control group). In our control group, telomeres of younger patients were significantly longer than telomeres of older ones. However, in HIV-infected participants, the difference in the length of telomeres was lost. By combining the length of telomeres with serum iron, ferritin, and transferrin iron-binding capacity, a new formula for determination of the aging process was developed. The life expectancy of the healthy population was related to their biological age, and HIV-infected patients were biologically older. The effect of antiretroviral HIV drug therapies varied with respect to the biological aging process. IMPORTANCE This article is focused on the dynamics of human aging. Moreover, its interdisciplinary approach is applicable to various systems that are aging.

The c.-1639G>A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy.

A single nucleotide polymorphism c.-1639G>A in the promoter region of vitamin K-epoxide reductase (VKORC1) gene has been found to account for most of the variability in response to oral vitamin K antagonist (VKA). Our aim was to study the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in a group of patients under stable anticoagulation, and to estimate the variability in response to VKA. We conducted a retrospective cohort analysis of 200 stable anticoagulation patients followed from the initiation of VKA. Out of 43 low-dose patients, 40 (93%) carried the A allele. The A allele was less frequent in the group of 30 patients requiring high VKA dose; among these patients 13 (43.3%) carried the A allele in the heterozygous form and none of them carried AA genotype. Patients with GG genotype required 2.6 times higher dose than patients carriers of AA genotype (P < 0.0001). Carriers of AA genotype were more likely to be overanticoagulated during follow-up after initiation of VKA when compared with carriers of the GA and GG genotypes (P < 0.0001). Patients with GG genotype spent more time below therapeutic range compared with patients carriers of AA (P = 0.0328) and GA genotype (P < 0.0001). VKORC1 c.-1639G>A polymorphism significantly influenced VKA dose and represented a good predictor of individuals predisposed to unstable anticoagulation. Pharmacogenetic testing could predict a high risk of overdose among 28.5% of our patients, carriers of AA genotype, before the initiation of anticoagulation.

[The c.-1639g > A polymorphism of the VKORC1 gene and his influence on the therapeutic response during oral anticoagulants use].

BACKGROUND/AIM: A single nucleotide polymorphism c.-1639G > A in the promoter region of vitamin K-epoxide reductase (VKORC1) gene has been found to account for most of the variability in response to oral anticoagulants (OA). The aim of the study was to determine the incidence and the effect of c.-1639G > A polymorphism on the acenocoumarol dosage requirements in the group of patients under stable anticoagulation, and to estimate the variability in response to OA. METHODS: Our study included 200 consecutive patients requiring low (n = 43), medium (n = 127) and high (n = 30) acenocoumarol dose. RESULTS: Out of 43 low dose patients, 40 (93%) carried the A allele. The A allele was less frequent in the group of 30 patients requiring high dose: among these patients 13 (43.3%) carried the A allele in the heterozygous form and none of them carried AA genotype. The patients with GG genotype required 2.6 times higher dose than the patients carriers of AA genotype (p < 0.0001). In 33 patients (16.5%) the overdose occurred during the initiation of anticoagulant therapy and in 11 patients (5.5%) it was associated with bleeding. Out of the group of 33 overdosed patients, 27 and 6 patients carried AA and GA genotype, respectively (p < 0.000001). CONCLUSION: VKORC1 significantly influenced OA dose and predicted individuals predisposed to unstable anticoagulation. The carriers of AA genotype required 2.6 time lower doses of OA than the carriares of GG genotype. Pharmacogenetic testing could predict a high risk of overdose among 28.5% of our patients--carriers of AA genotype, before anticoagulation therapy initiation.