Association of TLR4 Single-Nucleotide Polymorphisms and Sarcoidosis in Greek Patients

Abstract

The present study investigates the potential role of Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile single-nucleotide polymorphisms (SNPs) as risk factors in the development of sarcoidosis using a novel high-throughput microtiter well-based bioluminometric genotyping assay. One hundred and nineteen Greek patients with sarcoidosis and 209 control subjects were genotyped for the two SNPs of the TLR4 gene. The genotypes observed were in Hardy-Weinberg equilibrium. The heterozygote frequency for both SNPs in sarcoidosis group and control population was 13.4% (16/119) and 10.5% (22/209), respectively. The minor genotype was found to be the same for both sarcoidosis and control groups and similar to that found in other Caucasian populations. No significant association of Asp299Gly and Thr399Ile polymorphisms with increased susceptibility to sarcoidosis was found (p = 0.61 and odds ratio = 1.183). In conclusion, genotype data for the TLR4 Asp299Gly and Thr399Ile polymorphisms in the Greek population were found to be in linkage disequilibrium, and no contribution in the pathogenesis of sarcoidosis was established. Further, in course of the present study, we demonstrated a very simple and sensitive high-throughput bioluminometric assay for genotyping Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene.

Toll like receptors in diseases of the lung

“…A follow up study could not confirm the association with these specific polymorphisms, but did find a significant linkage between markers on the TLR4 gene locus and sarcoidosis [102]. Still other studies have failed to confirm the associations with Asp 299Gly or Thr399Ile in either Greek [103] or Dutch [104] populations. Likewise, no associations with TLR9 polymorphisms and sarcoidosis have been discovered, although decreased IFNγ production has been seen in response to TLR9 stimulation in peripheral blood mononuclear cells of sarcoidosis patients [105].…”

Genotype Frequency of the Common TLR4 SNPs in a Kurdish Population: Global Reviews and Out-of-African Migrations

“…As some early humans passed through and settled in the Middle East on their paths out of Golovkin et al 2015;Gowin et al 2017;Greene et al 2009;Hamann et al 2005;Heesen et al 2003;Iliadi et al 2009;Jabłońska et al 2020;James et al 2007;Jedlińska-Pijanowska et al 2020;Karananou et al 2019;Koch et al 2006;Kutikhin et al 2014;Lammers et al 2005;Marchionni et al 2020;Molvarec et al 2008;Mrazek et al 2013;Nedoszytko et al 2018;Noack et al 2008;Perica et al 2015;Piñero et al 2017;Rigoli et al 2008Rigoli et al , 2010Rybka et al 2016;Salpietro et al 2011;Sanders et al 2013;Sheedy et al 2008;Soriano-Sarabia et al 2008;Varzari et al 2019;Verweij et al 2016;Wujcicka et al 2015aWujcicka et al , 2015bWujcicka et al , 2017a almost all populations in the world, whereas the heterozygous variants, Asp299Gly and Thr399Ile, varied among populations. For instance, their genotype frequency percentages were 14.3% and 1.6%, respectively, in sub-Saharan populations but were 11.3% and 6.8% in North African people.…”

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

“…The exact prevalence of both SNPs in the Greek population is largely unknown since only a handful of studies regarding that issue exist. In these studies, the prevalence of Asp299Gly and Thr399Ile SNPs range, in various populations, from 5–25% and from 2–13%, respectively [ 38 , 39 , 40 , 41 ].…”