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The multifactorial pathogenesis of severe malaria is partly attributed to host genes, such as those encoding cytokines involved in complex inflammatory reactions, namely tumor necrosis factor-alpha (TNF-α). However, the relationship between TNF-α -308G >A gene polymorphism (rs1800629) and the severity of Plasmodium falciparum (P. falciparum) malaria remains unclear, which prompts a meta-analysis to obtain more precise estimates. The present meta-analysis aimed to better understand this correlation and provide insight into its association in populations with different ethnicities. Literature search outcomes included eight eligible articles in which TNF-α -308G >A polymorphism was determined in uncomplicated malaria (UM) and severe malaria (SM) of P. falciparum as represented in the case and control groups. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated in standard homozygous, recessive, dominant, and codominant genetic models. Subgroup analysis was based on ethnicity, i.e., Africans and Asians. The analyses included overall and the modified outcomes; the latter was obtained without the studies that deviated from the Hardy-Weinberg Equilibrium. The significant data also underwent sensitivity treatment but not publication bias tests because the number of studies was less than ten. Interaction tests were applied to differential outcomes between the subgroups. Overall and HWE-compliant analyses showed no significant association between the TNF-α -308G >A polymorphism and susceptibility to P. falciparum SM (ORs = 1.10–1.52, 95%CIs = 0.68–2.79; Pa = 0.24–0.68). Stratification by ethnicity revealed that two significant associations were found only in the Asians favoring SM for dominant (OR = 1.95, 95% CI = 1.06–3.61, Pa = 0.03) and codominant (OR = 1.83, 95% CI = 1.15–2.92, Pa = 0.01) under the random-effects model, but not among the African populations. The two significant Asian associations were improved with a test of interaction with P-value of0.02–0.03. The significant core outcomes were robust. Results of the meta-analysis suggest that TNF-α -308G >A polymorphism might affect the risk of P. falciparum SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the TNF-α -308G >A association with the clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion. Author summary: Host genetic factors play important role in the development and progress of severe malaria due to Plasmodium falciparum infection. One of the key factors is the abnormality in the gene that encodes cytokines, particularly tumor necrosis factor-alpha (TNF-α), which are involved in complex inflammatory reactions. However, the relationship between the abnormality of this gene and malaria severity remains unclear. The present meta-analysis aimed to better understand this correlation and provide insight into its association in populations with different ethnicities. The analyses showed no significant association. Stratification by ethnicity revealed that two significant associations were found only in the Asians favoring SM for dominant and codominant, but not among the African populations. Results of the meta-analysis suggest that TNF-α -308G >A might affect the risk of P. falciparum SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the association between the abnormality of this gene and clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate associations between polymorphisms in the Lysyl oxidase (LOX) gene with susceptibility to cancer. The role of LOX in carcinogenesis prompted several association studies in various cancer types; however the outcomes of these studies have inconsistent. Thus, we performed a meta-analysis to obtain more precise estimates. Materials and Methods: A literature search yielded 14 articles from which we examined five cancer groups: breast, bone, lung, gastrointestinal, and gynecological cancers. For each cancer group, pooled odds ratios (ORs) and confidence intervals (95% CIs) were calculated using standard genetic models. High significance (p-value for association [pa] < 0.00001), homogeneity (I2 = 0%), and high precision of effects (CI difference [CID] <1.0 [upper CI − lower CI]) comprised the three criteria for strength of evidence. We used sensitivity analysis to assess robustness of the outcomes. Results: We generated 28 comparisons from which 13 were significant (pa < 0.05), indicating increased risk, (OR >1.00) found in all cancer groups except breast (pa = 0.10–0.91). Of the 13, three met all criteria (core) for strength of evidence (pa < 0.00001, CIDs 0.49–0.56 and I2 = 0%), found in dominant/codominant models of gynecological cancers (ORs 1.52–1.62, 95% CIs 1.26–1.88) and codominant model of lung cancer (OR 1.44, 95% CI 1.19–1.74). These three were deemed robust. Conclusion: Based on the three core outcomes, associations of LOX 473G/A with lung, ovarian, and cervical cancers indicate 1.4–1.6-fold increased risks, underpinned by robustness and high statistical power at the aggregate level. [ABSTRACT FROM AUTHOR]

Purpose: Reported associations of interleukin-18 (IL-18) single-nucleotide polymorphisms (SNPs) with allergic rhinitis (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. Methods: We synthesized data from 8 articles and examined 3 IL-18 SNPs. Two SNPs (rs360721 and rs187238), in linkage disequilibrium, were combined and termed RS1. The rs1946518 SNP was analyzed separately (termed RS2). The recessive, dominant, and codominant (multiplicative) genetic models were used to estimate ORs and 95% CIs. Subgroup analysis was ethnicity-based. Sources of heterogeneity were investigated with outlier treatment. Sensitivity analysis was used to assess robustness of the associative effects. Multiple comparisons were Holm-Bonferroni corrected. Results: All significant (pa < 0.05) outcomes indicating increased risks were found in the dominant/codominant models in RS1 and RS2. Five aspects of differences marked the significant African (RS1) and overall (RS2) outcomes: (i) magnitude of effect (ORs): greater (3.01–5.15) versus less (1.20–1.47); (ii) precision of -effects (95% CIs): less (1.07–21.52) versus more (1.01–1.89); (iii) outlier treated: no versus yes; (iv) sensitivity outcomes: nonrobust versus robust (dominant model only); and (v) greater evidential strength for RS2 (pa = 0.002) compared to RS1 (pa = 0.02) rendered RS2 our core finding. These levels of statistical significance for RS1/RS2 enabled both to survive the Holm-Bonferroni correction. Conclusions: The core outcome indicating a 1.5-fold increased risk could render the IL-18 polymorphisms useful in the clinical genetics of AR. Future studies that could focus on other IL-18 SNPs may find deeper associations with AR than what we found here. [ABSTRACT FROM AUTHOR]