RESUMEN
Seeking human longevity association with gene polymorphisms in transcription factors in the Tatar ethnic group, we conducted an analysis for age-related genotype, frequencies in polymorphic sites of FOXO1A (rs4943794, 72327C>G) and FOXO3A (rs3800231, 35-2764A>G) genes. Genotyping was conducted by using the PCR-RFLP approach. According to the results of logistic regression analysis, during maturity and old age periods, a decrease in the number of FOXO1A*G/*G (OR = 0.984, P = 0.004) genotype carriers occurs and an increase in the number of FOXO1A*C/*G (OR = 1.035, P = 0.014) and FOXO1A*C/*C (OR = 1.024, P = 0.033) genotype carriers occurs in the sample of subjects before gender adjustments. In the sample of long-livers, the number of FOXO1A*C/*C (OR = 0.772, P = 0.028) genotype carriers decreased among women, while the number of FOXO3A*G/*G (OR = 1.008, P = 0.0001) genotype carriers increased among both men and women. Therefore, the FOXO1A gene polymorphic site rs4943794 is associated with an acquisition of old and senescent age in a sample before gender adjustments and with women's longevity. FOXO3A gene polymorphic site rs3800231 is associated with longevity in both women and men.
Asunto(s)
Factores de Transcripción Forkhead/genética , Estudios de Asociación Genética , Longevidad/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The distribution of allele and genotype frequencies of Alu(I/D) polymorphic sites in the COL13A1 and LAMA2 genes coding extracellular matrix protein subunits was characterized in an ethnically homogeneous group (Tatars from the Republic of Bashkortostan, Russia). It was established that the frequency of individuals with the COL13A1*D/*D genotype was higher in the senile age period. The LAMA2*I/*D genotype was predisposing to longevity among women. According to the observed results, the frequency of the LAMA2*I/*D genotype was increased in senile individuals older than 90 years. The observed associations can be explained on the basis of the contemporary view by the importance of Alu elements in gene expression regulation at transcriptional and post-transcriptional levels, the involvement of collagen and laminin in maintaining the structure and function of the extracellular matrix, and the relationship between the extracellular matrix state, pathological changes and aging.
Asunto(s)
Elementos Alu , Colágeno/genética , Mutación INDEL , Laminina/genética , Longevidad/genética , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Colágeno/biosíntesis , Femenino , Regulación de la Expresión Génica , Humanos , Laminina/biosíntesis , Masculino , Persona de Mediana EdadRESUMEN
This review is devoted to the description of research achievements in genetics of aging and longevity. It represents a certain interest for understanding of a problems of aging as a whole. There is a huge amount of results of diverse genetic studies of aging and longevity. Studies were performed with using different experimental strategies on model organisms or samples from different human populations of the world. The search for aging and longevity genes was carried out within international consortiums. The first results of whole genome sequences of super-centenarians were received. The genes influencing life expectancy were revealed in organisms of different systematic groups. Many of these genes are evolutionarily conservative. Associations between APOE, FOXO1A, FOXO3A, AKT1 gene polymorphisms and human longevity were confirmed in independent studies.
Asunto(s)
Envejecimiento/genética , Esperanza de Vida , Longevidad/genética , Biología Molecular/métodos , Anciano de 80 o más Años , HumanosRESUMEN
The allele and genotype frequency distribution at polymorphic loci rs3892097 (184G>A) of CYP2D6 gene, rs776746 (6986A>G) of the CYP3A5 gene and rs2740574 (-392A>G) of the CYP3A4 gene in Russians, Tatars, and Bashkirs was examined. Samples were taken from residents of Bashkortostan Republic (1240 men and women aged from 20 to 109 years and consisted of 443 Russians, 517 Tatars, and 280 Bashkirs). Allele identification was conducted using PCR-RFLP or PCR with TaqMan probes. The "nonfunctional" allele rs3892097*A of the CYP2D6 gene was detected in populations of Russians, Tatars, and Bashkirs in 17.2, 9.5, and 7.1% cases, respectively. The rs776746*G allele of the CYP3A5 gene encoding the CYP3A5 isoenzyme with decreased activity was revealed with a frequency of 94.6% in populations of Russians, 94.3% in the Tatar population, and 91.5% in the Bashkir population. The share of the minor allele rs2740574*G of the CYP3A4 was 4.0% in populations of Russians, 0.5% in the Tatar population, and 0.9% in the Bashkir population. It has been previously shown that the rs3892097*A, rs776746*G, and rs2740574*G allele frequencies vary significantly in different world populations. Since allele variants of CYP2D6, CYP3A5, and CYP3A4 genes can play essential role in interindividual and in interethnic differences in the metabolism of many therapeutic agents, the obtained results could be used in the prognosis of pharmacotherapy efficacy in populations of Russians, Tatars, and Bashkirs.
