Toll-like receptor gene polymorphisms in patients with keratitis

Abstract

Objective: To investigate differences in SNPs in TLR genes between people who had keratitis and controls in an Indian population.

Methods: 145 cases of keratitis and 189 matched controls were recruited. DNA was extracted from peripheral blood. Single nucleotide polymorphisms (SNP) in TLR2 (n = 6), TLR4 (n = 15), TLR5 (n = 13) and TLR9 (n = 10) were analysed. The risk of developing keratitis was assessed based on allele, genotype and haplotype associations.

Results: For all cases of keratitis, the TLR4 SNP rs4986791 TC genotype frequency was significantly higher in cases (p = 0.006, OR = 1.96, 95 % CI 1.19-3.2). Including cases of only microbial keratitis (MK) revealed that genotypes in TLR2 SNP rs5743706 TA (p = 0.0001; OR = 8.61; 95 % CI 2.59-28.56)), TLR4 SNP s4986791 TC (p = 0.002; OR = 2.65; 95 % CI 1.39-5.07) were significantly more common for MK, whereas the TLR5 SNP rs2241096 A allele (p = 0.00316, OR = 0.42, 95 % CI 0.2-0.9286) and GA genotype (p = 0.016; OR = 0.45; 95 % CI 0.23-0.86) was significantly less common in MK cases. The TLR2 SNP rs5743706 genotype TA was significantly less common in the sterile keratitis (SK) group (p = 0.004, OR = 0.43, 95 %CI 0.24-0.77). Haplotype analysis of MK compared to controls showed that TLR2 AT was more common in controls (p = 0.003); TLR4 ACAC was more common in cases (p = 0.004); TLR5 TGGCA was more common in controls (p = 0.001).

Conclusion: The present study revealed multiple associations between variants across TLR genes, which may have implications for understanding the underlying host factors, risk of developing keratitis and molecular pathogenesis in keratitis.

Keywords: Genotype; Keratitis; SNP; Toll-like receptor.