Longevity and carrying the C282Y mutation for haemochromatosis on the HFE gene: case control study of 492 French centenarians

摘要

Hereditary haemochromatosis is a common auto-somal recessive disorder of iron metabolism. Most patients are homozygous for a C282Y mutation in the HFE gene. This mutation is frequent in northern Europe, where one in five to ten people are carriers. People who are heterozygous for the C282Y mutation have slightly but significantly higher values for serum iron and transferrin saturation and are less likely to have anaemia because of iron deficiency. Iron promotes the generation of free radicals, which leads to mutagenesis, atherosclerosis, inflammation, and bacterial growth. Therefore, genotypes that increase the concentrations of iron for transport and storage may be associated with an increased risk for common diseases, such as cancers and cardiovascular diseases, and for inflammatory and infectious conditions. Other studies, which investigated the associations of C282Y heterozy-gosity with morbidity, found conflicting results, and consensus has not been reached about whether C282Y is associated with the development of extrahepatic cancers, coronary heart disease, or diabetes. We hypothesised that people who are heterozygous for the C282Y mutation are under-represented in a centenarian population because many would have died younger from life threatening diseases which are more prevalent in C282Y heterozygotes.