Abstract
To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic.
Highlights
Trachoma disease is characterized by repeated episodes of Gramnegative Chlamydia trachomtis (Ct) infections
Genetic polymorphisms in Toll like receptor 4 (TLR4) and Major histocompatibility complex (MHC) class I chain related gene (MICA) might be associated with host immunity to Trachoma disease and its subclinical phenotypes. Since their alleles vary among individuals and may confer variable disease susceptibilities, understanding the significant role that MICA and TLR4 alleles play in host inflammatory response is useful in research studies on inflammatory diseases
The MICA-A9 allele was found to be statistically significant in both TI (OR=0.63 95% CI: 0.4164-0.9532, p= 0.0520) and trachomatous trichiasis (TT) (OR=0.53 95% CI: 0.3306-0.8496, p=0.0239) groups when compared to the control group (TN) (Table 1)
Summary
Trachoma disease is characterized by repeated episodes of Gramnegative Chlamydia trachomtis (Ct) infections. The infection causes a chronic inflammatory and immune fibrogenic process leading to conjunctival scarring and blinding squeal [1]. 84 million individuals worldwide have active infections; 1.2 million are estimated to have visual impairment, and 3% to have blindness [2,3]. The ocular disease progresses through five stages, which may overlap with increasing severity. These phases include trachomatous inflammation, follicular (TF), trachomtous inflammation, intense (TI), trachomatous scarring (TS), trachomatous trichiasis (TT), and corneal opacity (CO). According to this classification, the first two grades TF and TI represent acute infection, whereas the other three grades represent the chronic stage of the disease [4,5]
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