Mapping leprosy-associated coding variants of interleukin genes by targeted sequencing

Area of Science:

• Genetics
• Immunology
• Infectious Diseases

Background:

• Non-coding variants of interleukins (ILs) have been linked to leprosy susceptibility.
• The role of coding variants in IL genes regarding leprosy risk remains largely unexplored.

Purpose of the Study:

• To comprehensively analyze the mutation spectrum of all IL family genes in leprosy.
• To identify specific coding variants associated with leprosy risk and their expression patterns.

Main Methods:

• Targeted deep sequencing of 58 IL genes in 798 leprosy patients and 990 healthy controls from Southwest China.
• Analysis of mRNA expression data of ILs in leprosy skin lesions and in response to Mycobacterium leprae stimulation.

Main Results:

• Two coding variants, rs17855750 in IL27 (p.S59A) and rs45507693 in IL1RN (p.A106T), were significantly associated with increased leprosy risk.
• mRNA levels of IL27 and IL1RN were found to be upregulated in whole blood cells following M. leprae stimulation.

Conclusions:

• Interleukin 27 (IL27) and Interleukin 1 receptor antagonist (IL1RN) are identified as novel leprosy risk genes.
• Further functional studies are warranted to elucidate the precise mechanisms by which IL27 and IL1RN contribute to leprosy pathogenesis.