HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish

Area of Science:

• Immunogenetics
• Human Leukocyte Antigen (HLA) Polymorphism
• Autoimmune Disorders and Aging

Background:

• Human leukocyte antigen (HLA) polymorphism is linked to autoimmune diseases and aging.
• Previous studies suggested an association between the HLA-A1, B8, DR3 haplotype and aging in males.
• Tumor necrosis factor (TNF) gene cluster polymorphisms (G-308A TNF-alpha and G+252A TNF-beta) are associated with increased TNF-alpha production.

Purpose of the Study:

• To investigate the association of the HLA-A1, B8, DR3 haplotype with aging in a male Irish population.
• To examine the linkage disequilibrium between TNF gene cluster polymorphisms and HLA loci.
• To determine if age-related allele or genotype frequencies exist for TNF polymorphic nucleotides.

Main Methods:

• Genotyping of HLA loci and TNF cluster polymorphic nucleotides (G-308A TNF-alpha, G+252A TNF-beta).
• Analysis of allele and genotype frequencies in a male Irish aged population.
• Assessment of linkage disequilibrium between HLA and TNF loci.

Main Results:

• No association was found between the HLA-A1, B8, DR3 haplotype and the male Irish aged population.
• The G-308A TNF-alpha and G+252A TNF-beta polymorphisms were in tight linkage disequilibrium with class I and II HLA loci.
• No age-related allele or genotype frequencies were observed for the studied TNF polymorphic nucleotides.

Conclusions:

• The previously reported association of the HLA-A1, B8, DR3 haplotype with aging in males was not replicated in this Irish cohort.
• Extended linkage disequilibrium exists between TNF gene cluster polymorphisms and HLA loci.
• Age does not appear to influence the allele or genotype frequencies of these specific TNF polymorphisms.