Single Nucleotide Variants in the TLR1, TLR2 and TLR6 Genes: A Case-Control Study in a Colombian Population

Area of Science:

• Immunogenetics
• Infectious Diseases Epidemiology

Background:

• Single nucleotide variants (SNVs) in toll-like receptor (TLR) genes are implicated in modulating immune responses, influencing susceptibility or resistance to infectious diseases like leprosy.
• Understanding the genetic basis of leprosy is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To investigate the association between specific SNVs in Toll-like Receptor 1 (TLR1), TLR2, and TLR6 genes and overall susceptibility to leprosy.
• To evaluate the role of a specific CGG haplotype across these TLR genes in leprosy development.

Main Methods:

• An epidemiology case-control study was conducted with 114 leprosy cases and 456 controls.
• Genotyping of SNVs (rs5743618 in TLR1, rs5743708 in TLR2, and rs5743810 in TLR6) was performed using TaqMan probes on DNA extracted from peripheral blood.
• Statistical analyses included estimation of associations under different inheritance models and haplotype analysis.

Main Results:

• The A/G genotype of rs5743810 in TLR6 demonstrated a protective effect against leprosy development in codominant, over-dominant, and dominant inheritance models.
• SNVs rs5743618 (TLR1) and rs5743708 (TLR2) showed no significant association with leprosy susceptibility.
• The CGG haplotype (rs5743618-rs5743708-rs5743810) was identified as a susceptibility factor for leprosy, particularly in women.

Conclusions:

• Genetic variants in TLR6 (rs5743810) and the CGG haplotype may contribute to leprosy susceptibility in the studied Colombian population.
• These findings highlight the role of specific toll-like receptor gene variants in the immunogenetics of leprosy.