Micronuclei and chromosomal aberrations, important markers of ageing: possible association with XPC and XPD polymorphisms.
Life expectancy in central-Eastern European countries is more than 10 years lower compared with Northern or Western countries which could be the result of complex factors including genetics, nutrition and life style. We conducted a molecular epidemiological study with the aim of investigating links between DNA instability, genetic polymorphisms in nucleotide excision repair genes and ageing. Two groups-151 young people (78 women and 73 men) aged 20-25, and 140 elderly subjects (101 women and 39 men), aged 65-70 have been investigated. Results show elevated levels of micronuclei and chromosome aberrations in elderly compared with young groups (P<0.001); women had more micronuclei than men (P<0.001). Micronucleus frequencies were influenced by age (P<0.001). In the group of elderly people those who were homozygous with C/C or A/A in XPC IVS11 had more aberrant cells compared with C/A heterozygotes (P=0.04). When the dependent variable was break per cell, elderly people A/A homozygous in XPC IVS11 had more breaks per cell compared with C/A heterozygous or C/C homozygous subjects (P=0.03). Significantly the most chromatid breaks were found in elderly people both Lys/Lys homozygous in the XPD Lys751Gln genotype and C/C or A/A homozygous in the XPC IVS11 genotype (P<0.05). A General Linear Model analysis shows a statistically significant effect of interactions between age, sex and genotype XPC IVS11 (P=0.001) and age, sex and genotype XPCin9 (P=0.007) on number of chromatid breaks. When we divided people into two subgroups (without mutant allele and with one or two mutant alleles) we found a significantly higher number of chromosome exchanges in people with one or two variant polymorphism XPCin9 (P=0.04), XPC IVS11 (P=0.004) or XPCex15 (P=0.001). Level of cells with micronuclei was influenced by polymorphisms XPD Lys751Gln (P=0.03). However, we did not find any relationship between XPA polymorphism and studied cytogenetic biomarkers.
Kazimírová
Alena
A
Research Base of the Slovak Medical University, Limbová 14, 833 01 Bratislava, Slovak Republic. alena.kazimirova@szu.sk
Barancoková
Magdaléna
M
Dzupinková
Zuzana
Z
Wsólová
Ladislava
L
Dusinská
Mária
M
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D002869:Chromosome Aberrations; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C086984:XPC protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human