engleski

Genotype and haplotype analysis of TP53 and health related traits in Croatian senescent population

The TP53 gene has been suggested to be associated with various diseases and with longevity due to its important functions in preserving the genome integrity. In this study we investigated the association of two polymorphisms of TP53 gene - Arg72Pro and PIN3 (+16bp) - with health related traits in 324 persons of very old age (85-101 yrs). The results showed that the health status in elderly is sharply discriminated by PIN3 (+16bp) genotypes: carriers of A1A2 or A2A2 genotype more frequently have cardiovascular diseases (CVD), osteoporosis, risk for undernutrition (weight loss, diarrhea), and they also recently suffered from stress or acute illness. In contrast, for the carriers of A1A1 genotype none disadvantageous condition could be detected. The Arg72Pro polymorphism differentiated the study participants as follows: ArgArg carriers showed more frequently CVD while ArgPro and ProPro carriers had lower body mass index and they more frequently suffered from stress or acute illness. Further analysis showed that the most frequent haplotype ArgArg_A1A1 (48.9% of all haplotypes), although very advantageous for many traits is characterized by increased fasting glucose levels or/and diabetes. The remaining two A1A1 haplotypes (ProPro_A1A1 and ArgPro_A1A1) have lower frequency of CVD and CVD risk factors as well as of osteoporosis ; the only disadvantageous characteristic being an increased risk for undernutrition. The present preliminary study exposes A1A1 genotype as the most advantageous TP53 genotype while A2 allele (A1A2 and A2A2 genotypes) bears substantial risk for various health related traits and it is so irrespective of codon72 status.

TP53; polymorphisms; health; ageing; longevity

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