Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Identification of immunogenetic factors (HLA and cytokine gene polymorphisms) involved in successful aging

Genetic epidemiology studies were performed on samples from randomly selected healthy elderly individuals (age 66-99 years) compared to unrelated young controls (age 21 - 35 years) and families with longevity members from the Bulgarian population.

The following genetic markers were analyzed: HLA class I (A, B) and class II (DRB) loci, IL-2, IL-6, IL-10, IL-12B, IFNã, TNF-A, and TGF-B1 genes. Additionally, HLA-DQB1 and DPB1 polymorphism was assessed in samples selected based on their HLA and cytokine gene profiles. Allele and haplotype frequency analyses were performed in order to identify alleles and extended haplotypes associated with immunosenescence. Prevalence of protective for autoimmune diseases DRB1*1101 and DRB1 x 1601 associated haplotypes was observed in healthy elderly Bulgarians. IL-10 -1082, -819, -519 genotypes related to a high level of expression were also positively associated with longevity in Bulgarians.

Additionally, investigation of extended profiles based on several SNPs in TNF-A gene with possible relation to the level of expression revealed decreased pro-inflammatory genotypes in elderly individuals. Extended genotypes, including several polymorphic positions of IL-12B and TGF-B1 relevant for successful aging were identified. Significance of the observed IL-12B genotypes was further confirmed in samples from the Italian population.

Additionally, new single nucleotide polymorphisms were identified in the prompter and intron 1 regions of TNF-A with possible functional significance. Sequences of these new gene variants are available.

A set of data concerning genetic background of aging is provided and genetic markers associated with successful aging are identified. These data will allow drawing conclusions on a correlation between gene variants and human longevity and will contribute to formulation of recommendations for biomarkers with possible clinical relevance.

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