Study of the Toll-like receptor 4 gene polymorphisms in diseases presenting with subclinical and chronic inflammation

Abstract

Toll-like receptor 4, a central mediator of the innate immune response has been shown to play an important role not only in the defense mechanism against microorganism, but also other non-infectious inflammatory diseases such as atherosclerosis. The Asp299Gly and Thr399Ile, which are common co-segregation polymorphisms of the Toll-like receptor 4 gene have been shown to be associated with increased susceptibility for Gram-negative infections, but with a lower risk of carotid atherosclerosis and a reduced level of certain proinflammatory cytokines. The role of these polymorphisms in diabetes mellitus with its late microvascular complications, in ischemic stroke, and in chronic periodontitis was investigated in three independent studies. In all studies the alleles of both polymorphisms were detected by polymerase chain reaction and subsequent cleavage by restriction endonucleases followed by gel electrophoresis. In patients with type 2 diabetes, heterozygote carriers of the Asp299Gly and Thr399Ile polymorphisms of the Toll-like receptor 4 gene had a significantly reduced prevalence of peripheral neuropathy, while there was no association with any other diabetic microvascular complication, or with cerebral ischemia or with chronic periodontitis. Toll-like receptor 4 gene polymorphisms are not enough sensitive genetic markers for risk stratification either in diabetes mellitus or in cerebral ischemia or in chronic periodontitis.