Rarity of TLR4 Asp299Gly and Thr399Ile Polymorphisms in the Korean Population

Abstract

PurposeActivation of the innate immune system and chronic low-grade inflammation are thought to be involved in the pathogenesis of atherosclerosis and also thought to be associated with type 2 diabetes and its complications. As a receptor for bacterial lipopolysaccharide and heat-shock proteins, Toll-like receptor 4 (TLR4) is one of the central regulators of the immune response. Recent studies have reported an association between TLR4 polymorphisms and diabetes and its complications in Caucasian populations.Materials and MethodsIn this study, we analyzed the association between TLR4 gene polymorphisms in patients with features of type 2 diabetes and healthy controls in Korea. Two polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) were examined in 225 diabetic patients and 153 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and single-strand conformation polymorphism (SSCP).ResultsNo Asp299Gly or Thr399Ile mutations were detected in any of the 378 subjects. Seven subjects from each group who had slightly different SSCP patterns were selected for sequencing, but we found no TLR4 polymorphisms on Exon3. The Asp299Gly and Thr399Ile TLR4 gene polymorphisms were absent in both groups, which was similar to the results for Japanese and Chinese Han subjects.ConclusionOur data and other Asian data suggest that a racial difference can be found in the frequency of the TLR4 polymorphism.

Genetic polymorphisms of the TLR4 gene and their association with susceptibility to type 2 diabetes mellitus in the Chinese population

“…To date, several single nucleotide polymorphisms (SNPs) have been identified in the human TLR4 gene (Raby et al, 2002;Kolz et al, 2008;Arora et al, 2011;Jiang et al, 2013), such as Asp299Gly (Rudofsky et al, 2004;Kim et al, 2008;Buraczynska et al, 2009;Arora et al, 2011;Maldonado-Bernal et al, 2011;Jiang et al, 2013) and Thr399Ile (Rudofsky et al, 2004;Kim et al, 2008;Kolz et al, 2008;Buraczynska et al, 2009;Maldonado-Bernal et al, 2011;Jiang et al, 2013). Furthermore, several studies proved that the TLR4 gene variants were associated with susceptibility to T2DM (Rudofsky et al, 2004;Kim et al, 2008;Kolz et al, 2008;Buraczynska et al, 2009;Arora et al, 2011;Maldonado-Bernal et al, 2011;Jiang et al, 2013). However, the data from these studies are inconsistent, and the exact mechanism is poorly understood.…”

“…Recently, studies reported that there is a very high T2DM incidence in China where diabetes has become a major public health problem (Yang et al, 2010), with approximately 92.4 million adults with the disease and 148.2 million with prediabetes (Jiang et al, 2013). A large number of previous studies have shown that the human Toll-like receptor 4 (TLR4) is potentially an important gene influencing the susceptibility to T2DM (Illig et al, 2003;Rudofsky et al, 2004;Creely et al, 2007;Kim et al, 2008;Buraczynska et al, 2009;Arora et al, 2011;Maldonado-Bernal et al, 2011;Jiang et al, 2013). To date, several single nucleotide polymorphisms (SNPs) have been identified in the human TLR4 gene (Raby et al, 2002;Kolz et al, 2008;Arora et al, 2011;Jiang et al, 2013), such as Asp299Gly (Rudofsky et al, 2004;Kim et al, 2008;Buraczynska et al, 2009;Arora et al, 2011;Maldonado-Bernal et al, 2011;Jiang et al, 2013) and Thr399Ile (Rudofsky et al, 2004;Kim et al, 2008;Kolz et al, 2008;Buraczynska et al, 2009;Maldonado-Bernal et al, 2011;Jiang et al, 2013).…”

TLR4 inactivation protects from graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

“…[15][16][17][18][19] The TLR4 Asp299Gly polymorphism, in particular, is the highest in African Americans, while in a western Iran population, the highest incidence for a mutation was found for the TLR4 Thr399Ile polymorphism, which is in, contrast, very rare in Asian populations, such as those in Japan and South Korea. 20,21 Carriers of the Thr399Ile TLR4 gene mutation have a significantly increased risk of developing GVHD, 42% versus 15% of non-affected patients, whereas transplant-related mortality, overall survival rate and the incidence of infectious complications are not influenced by the mutated gene. 22 Histopathological changes in the small intestine are more severe in TLR4-mutant host GVHD recipients than those in TLR4-intact host GVHD recipients at 14 days after GVHD development, 23 but the studies reporting these results did not clearly demonstrate the role of TLR4 in the HSCT-related pathogenesis of GVHD.…”

Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis

“…Our literature search identified four studies that evaluated the Asp299Gly and Thr399Ile polymorphisms in Asian populations, but they could not be included in the present meta-analysis because only the ancestral genotypes were found [39][40][41][42]. The lower frequency of the minor alleles of these TLR4 polymorphisms in Asians will require larger sample sizes to detect any statistically significant association with T2DM.…”