Genetic polymorphism of human interleukin-1 alpha

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• Interleukin-1 alpha (IL-1 alpha) is linked to infectious, autoimmune, and inflammatory diseases.
• Limited information exists on IL-1 alpha gene regulation and structural variations.
• Intron 6 of the IL-1 alpha gene contains a known 5 x 46 bp tandem repeat.

Purpose of the Study:

• To investigate the polymorphism within the tandem repeat region of the IL-1 alpha gene.
• To characterize the allelic variation and frequencies of this repeat.
• To explore the potential functional implications of this polymorphism.

Main Methods:

• Polymerase chain reaction (PCR) amplification of the IL-1 alpha intron 6 region.
• DNA sequencing to identify repeat number variations.
• Restriction fragment length polymorphism (RFLP) analysis.
• Electrophoretic mobility shift assay (EMSA) to confirm protein binding.

Main Results:

• Variable sized PCR products indicated a polymorphism in the 46 bp tandem repeat sequence.
• Sequencing confirmed a variable number of repeats, with 6 alleles found in 72 individuals (5-18 repeats).
• The most frequent allele (62%) had 9 repeats.
• Each repeat contains potential binding sites for SP1, viral enhancers, and glucocorticoid-responsive elements, with demonstrated protein binding to the latter.

Conclusions:

• A novel polymorphism in the IL-1 alpha gene intron 6, characterized by a variable number of 46 bp tandem repeats, has been identified.
• This polymorphism, with its potential regulatory elements, may impact IL-1 alpha gene function.
• Further research is ongoing to determine the functional significance and allelic frequency in disease states.