Association between two tumour necrosis factor intronic polymorphisms and HLA alleles

Area of Science:

• Immunogenetics
• Human Genetics
• Molecular Biology

Background:

• The tumour necrosis factor (TNF) gene is located within the major histocompatibility complex (MHC) class III region.
• Polymorphisms in the TNF gene are associated with numerous human diseases.
• Previous studies identified TNF +489 and +691 polymorphisms but lacked linkage disequilibrium analysis with MHC alleles.

Purpose of the Study:

• To investigate the association between TNF gene polymorphisms (+489 and +691) and specific human leukocyte antigen (HLA) alleles (DR, DQ, and B).
• To determine the pattern of linkage disequilibrium between these TNF polymorphisms and MHC alleles in a healthy population.

Main Methods:

• Genotyping of TNF +489 (G to A) and +691 (G deletion) polymorphisms in 216 healthy individuals.
• Analysis of associations between identified TNF alleles and HLA-DR, -DQ, and -B alleles.
• Statistical analysis to assess linkage disequilibrium patterns.

Main Results:

• The frequencies of uncommon alleles were 0.08 for TNF +489A and 0.05 for TNF +691Gdel.
• TNF +489A allele showed association with DRB1*1104, DQB1*0301, B18, and B35.
• TNF +691Gdel allele was associated with DRB1*13*11, DQB1*0301, and B44.

Conclusions:

• Established associations indicate probable linkage disequilibrium between specific TNF alleles and MHC alleles.
• This knowledge is valuable for future studies investigating the role of TNF and MHC in disease etiology.
• Understanding these genetic associations can refine research into the genetic basis of complex diseases linked to MHC haplotypes.