Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China

Huang, Zhaohe; Liu, Yan; Lin, Limei; Liu, Wenjing; Sooranna, Suren R.; Mo, Jianjiao; Liu, Li; Li, Zhile; Guo, Jun

doi:10.1016/j.gene.2019.05.014

Cited by 2 publications

(3 citation statements)

References 46 publications

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“…A laboratory study by Sato et al revealed that a fragment of 3 ′ -UTR containing the TLR4 rs11536889 G allele, but not the C allele, inhibited luciferase activity triggered by LPS or IL-6 possibly by binding to miRNAs in posttranscriptional regulation [32]. Several studies found that TLR4 rs11536889 CC genotype or C allele was correlated with an increased risk of coronary artery disease [12], gastric cancer [33], and hepatitis A virus infection [34]. In this research, we figured out that female individuals carrying rs11536889 GC genotype or dominant model were more susceptible to AAD compared with those with GG genotype.…”

Section: Discussionmentioning

confidence: 99%

“…Toll-like receptor 4 (TLR4), located on chromosome 9q32-q33, is not only the key pattern-recognition receptor in immune-inflammatory reactions but also the initiation protein in this signal transduction pathway [12]. Recently, the role of TLR4-mediated signaling has emerged in maintaining aortic homeostasis and establishing the aorta alterations (vascular remodeling and medial degeneration) and their complications [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population

Liu

Ning

et al. 2020

BioMed Research International

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Background. Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD. Methods. A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3 ′ -untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects’ medical records, and serum TLR4 levels were collected from our previously published data. Results. We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393 , 95 % CI = 0.164 ‐ 0.939 , P = 0.036 ; recessive model: OR = 0.439 , 95 % CI = 0.196 ‐ 0.984 , P = 0.045 ) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382 , 95 % CI = 1.051 ‐ 10.885 , P = 0.041 ; dominant model: OR = 3.043 , 95 % CI = 1.041 ‐ 8.900 , P = 0.042 ). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD ( P interaction = 0.038 , OR = 15.229 ) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD ( P = 0.037 ), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers ( P = 0.043 ). Conclusions. Our findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population

Liu

Ning

et al. 2020

BioMed Research International

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“…Sun et al reported that the "C" allele was significantly associated with ventilator-associated pneumonia in the Chinese population [14]. Another study reported that the rs11536889 "C" allele increases the risk of coronary artery disease in ethnic Zhuang and Han Chinese populations [15,16]. Chang et al found that the G/C and C/C genotypes were associated with head and neck cancer in Taiwan's population [17].…”

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confidence: 99%

Analysis of the genetic diversity in TLR4 3'-untranslated region among Asian populations and the biological effects of altofrequent SNPs

Chen

Yang

Zhang

et al. 2019

Preprint

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Background: Numerous case-control studies have demonstrated that single nucleotide polymorphism (SNP) loci in the TLR4 3'-untranslated region (UTR) are associated with multiple inflammatory disorders in various populations, particularly in Asians. However, the distribution frequency of polymorphisms in different Asian races and its effects on TLR4 expression remain unclear. Here, we extracted variants from the 1000 Genomes project database and analyzed the SNPs and haplotypes genetic diversity of TLR4 3'-UTR in 10 Asian populations, and then assessed the biological effects of the altofrequent polymorphic loci on TLR4 expression by luciferase assay. Results: Total 6 SNPs were identified as true polymorphic loci with minor allele frequencies (MAFs) ≥ 1% in Asian populations, including rs41426344, rs7869402, rs11536889, rs7873784, rs11536891, and rs11536896. Considering 4 Tag SNPs, we inferred 5 haplotypes that present a Asiatic frequency higher than 1%. It is noteworthy that rs41426344 is unique to East Asian populations, and the H-5 haplotype frequency was reduced when analyzing pooled data from East and South Asian populations. The MAFs of rs7869402 and rs11536889, and H-2 and H-4 frequencies significantly differed between the populations (P < 0.001). We constructed a pGL3-3494-3UTR luciferase plasmid to simulate TLR4 gene structure in vivo, and used PCR-mediated site-directed mutagenesis to construct a series of mutant luciferase constructs corresponding to the six SNPs. In addition, we identified that TLR4 mRNA was selectively expressed in SiHa and THP-1 cell lines, but not in C33A, Hela, and 293T cell lines. The luciferase activity of constructs containing rs7869402 T allele and rs11536889 C allele increased significantly upon LPS or IL-6 stimulation in THP-1 and SiHa cells. Conclusions: The distributions of SNPs and haplotypes in TLR4 3'-UTR were significantly different among Asian populations. The biological effects of rs7869402 and rs11536889 on TLR4 are significant clues that revealing its critical role in harmful TLR4-mediated responses. These results provided a reminder for future investigation on TLR4 related inflammatory diseases susceptibility.

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Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China

Cited by 2 publications

References 46 publications

Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population

Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population

Analysis of the genetic diversity in TLR4 3'-untranslated region among Asian populations and the biological effects of altofrequent SNPs

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