Toll-like receptor gene polymorphisms in patients with keratitis. Issue 3 (June 2021)

• Record Type: Journal Article
• Authors: Konda, Nagaraju; Kaur, Inderjeet; Garg, Prashant; Chakrabarti, Subhabrata; Willcox, Mark D.P.
• Is Part Of: Contact lens & anterior eye. Volume 44:Issue 3(2021)
• Publication Date: 2021-06
• Subjects: Keratitis -- Genotype -- SNP -- Toll-like receptor; Anterior segment (Eye) -- Periodicals; Contact lenses -- Periodicals; Segment antérieur (Œil) -- Périodiques; Lentilles de contact -- Périodiques; 617.752305
• DOI: 10.1016/j.clae.2020.07.003
• Languages: English
• ISSNs: 1367-0484

Abstract

Highlights: People with keratitis were compared to controls to determine whether they had changes to genes encoding Toll-like receptors (TLRs). Several single nucleotide polymorphisms in TLRs 2, 4 and 5 were significantly different between the cases and controls. These differences may relate to susceptibility towards keratitis during contact lens wear. 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.