Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

Abstract

Classes I and II human leukocyte antigens (HLA) genes encode highly polymorphic heterodimeric glycoproteins involved in the control of immune responses. The HLA class I gene HFE seemingly no longer participates in immunity because it has lost its ability to bind peptides and it has acquired the ability to form complex with the receptor for iron-binding transferrin by regulating iron uptake by intestinal cells. Thus, it indirectly regulates immune responses too, because iron availability plays a role in specific and non-specific immune responses. The distribution of HFE polymorphisms in Sicilian centenarians and nonagenarians was studied to evaluate if HFE alleles might be represented differently in people selected for longevity. DNA samples were obtained from 106 young controls (age range from 22 to 55 years; 40 men and 66 women) and 35 elderly subjects (age range from 91 to 105 years; seven men and 28 women). Samples were typed for C282Y, H63D and S65C alleles using polymerase chain reaction and sequence specific primers. Among the young individuals, none was heterozygous for the C282Y or for S65C mutation. Twenty-six were heterozygous for H63D mutation. Among the elderly subjects, 11 were heterozygous for the C282Y mutation or for H63D mutation. None was heterozygous for the S65C mutation. No compound heterozygous individuals (C282Y/H63D) were found. A highly significant difference was observed in frequencies of C282Y alleles between the young and the elderly subjects on the whole. By analysing polymorphisms according to gender, heterozygous subjects for C282Y were found both in old men and in old women, but by comparing the allele frequencies to those of young people significance was attained only in women. Concerning H63D polymorphisms, no significant differences were observed, between old and young people, both in men and in women. Possession of C282Y allele, known to be associated with an increase of iron uptake, significantly increases women possibility to reach longevity. Thus, present data adds another piece of evidence to the complex puzzle of genetic and environmental factors involved in control of lifespan expectancy in humans.