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Association Between TLR4 Gene Polymorphisms and Risk of Preeclampsia: Systematic Review and Meta-Analysis.

ABSTRACT: BACKGROUND Toll-like receptor 4 (TLR4) plays a pivotal role in the innate immune response and is hyperactivated in preeclampsia (PE). Several researchers have published conflicting evidence for TLR4 rs4986790 and rs4986791 single nucleotide polymorphisms (SNPs) as risk factors for PE. The present meta-analysis was conducted to obtain a more definitive conclusion about the effects of these SNPs on PE susceptibility. MATERIAL AND METHODS To determine the correlation between rs4986790 and rs4986791 polymorphisms in the TLR4 gene and susceptibility to PE, the PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and Chinese WANFANG databases were searched for eligible articles. Statistical analysis was performed with STATA software, version 12.0. Pooled odds ratios with corresponding 95% confidence intervals (CIs) were extracted for assessment of correlation strength. RESULTS We identified 5 studies including 578 cases and 631 controls for the rs4986790 SNP and 4 studies including 469 cases and 457 controls for the rs4986791 SNP, mainly from a White population. The pooled analyses showed no statistical relationship between the polymorphisms rs4986790 and rs4986791 and PE susceptibility in 5 genetic models (all P>0.05). Moreover, the allelic and dominant gene models of rs4986790 and the allelic, heterozygous, and dominant gene models of rs4986791 had high heterogeneity. The sensitivity analysis explored potential sources of heterogeneity and confirmed the findings of this meta-analysis. CONCLUSIONS TLR4 rs4986790 and rs4986791 polymorphisms may not be implicated in PE susceptibility, primarily in a White population. More high-quality studies of genetic associations with PE are warranted.

SUBMITTER: Sun M

PROVIDER: S-EPMC8343538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Asthma is a common complex chronic, inflammatory polygenic disease with heterogeneous manifestations, affecting individuals of all age groups and posing an immense burden on healthcare resources. A number of studies have identified the association between a disintegrin and metalloprotease 33 (ADAM33) polymorphisms and asthma risk, however, the results still remain inconclusive. The objective of the present study was to identify the effect of ADAM33 variants in asthma susceptibility. METHODS:Eligible case-control studies published between January 2000 and June 2018 was searched and retrieved from online electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the effect. RESULTS:A total of 63 case-control studies were finally screened out, including 13,280 asthma patients and 13,340 controls. Eleven SNPs of ADAM33 gene were identified. Our results detected a significant association between ADAM33 T2, Q1, F?+?1 and AA genotype of T?+?1 polymorphisms and asthma risk in total population. Subgroup analysis by ethnicities showed that the alleles and genotypes of T2, Q1 and F?+?1 polymorphisms were associated with asthma susceptibility among Asian populations, while V4 polymorphism was associated with asthma among Caucasian populations. Subgroup analysis by ages showed that T2, F?+?1 and ST?+?4 polymorphisms were associated with childhood asthma, while Q1 and V4 polymorphisms were associated with asthma risk in adults. Subgroup analysis by asthma severity showed that only the G allele of ADAM33 T1 polymorphism was associated with the severity of asthma when compared with the controls. In addition, T2, Q1 and F?+?1 polymorphisms of ADAM33 were significantly associated with increased the asthma risk in Chinese asthma patients. CONCLUSIONS:Our results found that T2, Q1 and F?+?1 polymorphisms of ADAM33 gene might contribute to asthma risk. Future well-designed case-control studies with large population and more ethnicities are still needed to estimate the association.

Project description:BACKGROUND:Preeclampsia is a serious pregnancy-specific syndrome with incompletely understood pathogenesis. Previous study has demonstrated that the decreased CXCR2 in preeclamptic placentas may contribute to the development of preeclampsia. The role of single nucleotide polymorphisms (SNPs) of CXCR2 gene in the pathogenesis of preeclampsia remains largely unexplored. Thus, we aimed to investigate the association between polymorphisms of CXCR2 gene and preeclampsia in Han Chinese women. METHODS:Totally 481 pregnant women, including 243 controls and 238 patients with preeclampsia were recruited. The rs1126579 and rs2230054 polymorphisms in CXCR2 gene were tested using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:Significantly increased risk of preeclampsia was observed in the rs1126579 CC or TC/CC genotypes when compared with TT genotype (CC vs. TT: odss ratio [OR] = 2.11, 95% confidence interval [CI] = 1.18-3.76, p = 0.039; TC/CC vs. TT: OR = 1.89, 95% CI = 1.29-2.78, p = 0.001). Markedly higher risk of preeclampsia was found to be associated with rs1126579 TC genotype (TC vs. TT/CC: OR = 1.48, 95% CI = 1.04-2.12, p = 0.031). After stratification analysis, the different distribution of TC/CC genotypes was particularly significant in the severe preeclampsia group (OR = 2.15, 95% CI = 1.42-3.24, p < 0.01), the early-onset severe preeclampsia group (OR = 1.97, 95% CI = 1.14-3.42, p = 0.013), and the late-onset severe preeclampsia group (OR = 2.29, 95% CI = 1.39-3.78, p < 0.01). Besides, TC genotype carriers had a 1.55 fold increased risk of severe preeclampsia (95% CI = 1.06-2.27, p = 0.022) and a 1.80 fold increased risk of late onset severe preeclampsia (95% CI = 1.14-2.83, p = 0.01) than those of TT/CC genotype carriers. CONCLUSIONS:Our study suggests a genetic association between rs1126579 polymorphism in CXCR2 gene and increased risk of preeclampsia. These data provide a new clue for future investigation.

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Association Between TLR4 Gene Polymorphisms and Risk of Preeclampsia: Systematic Review and Meta-Analysis.

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