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Abstract
The PRNP gene encodes the cellular isoform of prion protein (PrPc). The M129V polymorphism influences the risk of prion diseases and may modulate the rate of neurodegeneration with age. We present the first study of the polymorphism among Polish centenarians. In the control group (n = 165, ages 18 to 56 years) the observed M129V genotype frequencies agreed with those expected according to the Hardy-Weinberg equilibrium (MM, MV, VV): 43%, 44%, 13% (HWE p > 0.05). Among centenarians (n = 150, ages 100 to 107) both homozygotes were more common than expected and HWE was rejected: 46%, 37%, 17% (expected 42%, 46%, 13%; HWE p = 0.025). This finding is consistent with a higher mortality rate among heterozygotes. However, the observed allele and genotype frequencies did not differ significantly between the oldest-old and the young controls. The genotypic frequencies were not related to severe cognitive impairment among the centenarians.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgements
The study was supported by the State Committee for Scientific Research (KBN) grants: No. PBZ-KBN-022/PO5/1999 (collection of samples and clinical characterization of centenarians), No. 2P05 B08430 (genotyping) and funds of Medical University of Lodz, No 503/1-034-04/503-01. Prof. Shirley Lindenbaum (Graduate Center City University of New York) is kindly acknowledged for assistance with preparation of the manuscript.