Functional significance of the Toll-like receptor 4 promoter gene polymorphisms in the Chinese Han population

Abstract Background: The toll-like receptor (TLR) genes were shown to be involved in the pathogenesis of RA. We aimed to investigate the genetic associations between the TLR-1, -2, -4, and -6 genes polymorphisms and RA susceptibility in a Chinese Han population. Methods : Six polymorphisms (TLR-1 (rs5743610, rs5743618), -2 (rs5743708), -4 (rs4986790, rs4986791), and -6 (rs5743810)) in TLRs genes were genotyped in 360 patients with RA and 560 matched healthy controls by using direct sequencing method. The ORs and 95% CIs were evaluated using a standard logistic regression analysis. Results : No significant association between the allelic, dominant and recessive models of TLR-1 rs5743618, TLR-2 rs5743708, TLR-4 rs4986790 and rs4986791, and TLR-6 rs5743810 polymorphisms and RA risk was observed (p>0.05). However, significant associations were detected between the allelic, dominant and recessive models of TLR-1 rs5743618 and RA risk (allelic: OR[95%CI]= 2.21 [1.73, 2.81], p<0.0001; dominant: OR[95%CI]= 2.33 [1.75, 3.09], p<0.0001; recessive models: OR[95%CI]= 3.70 [1.85, 7.41], p=0.0002), In addition, the TLR6 rs5743810 was found to be associated with the RF - and anti-CCP - antibody in RA group (RF: OR[95%CI]= 2.29 [1.42, 3.69], p=0.0007; anti-CCP: OR[95%CI]= 2.33 [1.39, 3.89], p=0.001). Conclusions : The allelic, dominant, and recessive models of TLR1 rs5743618 might be associated with RA susceptibility. And the TLR6 rs5743810 might be associated with RF and anti-CCP antibody in RA in Chinese Han population.

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

BioMed Research International ◽

10.1155/2020/8306903 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Tan Li ◽

Xiaozheng Liu ◽

Hongxia Ning ◽

Xintong Li ◽

Jun Yang ◽

...

Keyword(s):

Aortic Dissection ◽

Acute Aortic Dissection ◽

Recessive Model ◽

Chinese Han Population ◽

Dominant Model ◽

Toll Like Receptor ◽

Chinese Han ◽

Toll Like Receptor 4 ◽

Han Population ◽

Increased Risk

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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