Toll-like receptor-2 (TLR-2) rs111200466 variant offers protection against SARS-CoV-2 infections and mortality: a worldwide epidemiological correlation analysis.

Recently Toll-like receptor-2 has been shown to sense the envelope protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and initiate the production of inflammatory molecules. The expression and function of the TLR2 has been associated with several functional polymorphisms such as a 23 bp ins/del (rs111200466), Arg677Trp (rs121917864), and Arg753Gln (rs5743708). In the present study, we hypothesized that the TLR2 common functional variants would be associated with the worldwide incidence and mortality rate of SARS-CoV-2. The frequency of TLR2 polymorphisms and coronavirus disease-19 (COVID-19) were acquired from multiple databases, including genomAD, 1000 genome, dbSNP, and worldometer, respectively. The Spearman rank correlation coefficient analysis revealed a significant inverse correlation between the del allele of rs111200466 polymorphism with susceptibility to SARS-CoV-2 infection and related mortality at different times. In conclusion, the TLR2 rs111200466 minor allele (del) may be linked with susceptibility to SARS-CoV-2 infections and bad outcomes. However, further case-control studies in different populations are required to validate our observations.

TNF-α promoter variant (G-308A) is associated with susceptibility to P. falciparum infection and severe malaria: a meta-analysis and trial sequential analysis.

Tumor necrosis factor-alpha (TNF-α) plays an essential role in Plasmodium falciparum infection, with lower levels associated with susceptibility to infection and higher levels linked with organ failure in severe malaria. Genetic polymorphisms in the promoter region of the TNF-α gene (G-308A and G-238A) affect plasma TNF-α levels. Numerous case-control studies have been conducted to determine the possible association between TNF-α polymorphisms and susceptibility to malaria infection and clinical severity; however, the results are inconsistent. Various databases such as Google Scholar, Science Direct, PubMed, and Scopus were searched for relevant articles for the present meta-analysis. Data were extracted from the eligible studies based on inclusion and exclusion criteria. Meta-analysis was carried out with CMA v.3.3.070 software, and combined odds ratio, 95% confidence interval, and p values were calculated. Further, a trial sequential analysis was also performed to test whether enough number of case and controls have been enrolled to date to draw a valid conclusion. Allele (OR = 9.757, p value=.049) and heterozygous (OR = 8.98, p value=.016) comparison model revealed the TNF-α G-308A variant as a susceptible genetic factor for P. falciparum infection. Similarly, a significant association of TNF-α G-308A polymorphism with P. falciparum malarial severity was also observed (A versus G: OR = 1.761, p value = .000; and GG + GA versus GG: OR = 1.769, p value = .000). However, no association of TNF-α (G-238A) polymorphism was observed with infection and severity of P. falciparum or Plasmodium vivax malaria. TNF-α G-308A variant is associated with susceptibility to P. falciparum infection and clinical severity. However, further studies on different populations are required.

Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis.

BACKGROUND: The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. MATERIALS AND METHODS: Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. RESULTS: Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). CONCLUSIONS: IFN-γ +874 T>A variant is associated with predisposition to SLE development.

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis.

BACKGROUND: The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity. MATERIALS AND METHODS: The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger's regression analysis were used to assess publication bias. Q statistics and I2 test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model. RESULTS: Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE. CONCLUSIONS: IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.

The relationship of childhood trauma to nicotine dependence in pregnant smokers.

Pregnant women with high levels of nicotine dependence are the least likely to quit smoking spontaneously during pregnancy or to benefit from smoking cessation interventions. In the general population, there is increasing evidence of a relationship between smoking, nicotine dependence, and exposure to childhood trauma. We examined the relationship of childhood trauma to several measures of nicotine dependence and evaluated whether this relationship was mediated by major depressive disorder or depressive symptom severity in pregnant smokers. Moderate to extreme levels of childhood trauma were significantly related to smoking within 5 minutes or less of waking, and to the Behavioral Choice-Melioration, Negative Reinforcement, and Tolerance subscales of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) scale. The relationships between childhood emotional abuse and the WISDM-68 Total and Negative Reinforcement subscale were partially mediated by depressive symptoms. Results suggest that childhood trauma may be a risk factor underlying nicotine dependence in pregnant smokers. Increased understanding of the relationship of affect regulation to smoking in individuals with childhood trauma histories may aid in the development of more effective treatments of nicotine dependence for this population of smokers.