Investigation of the linkage between TNF-alfa rs1800629 polymorphism and preeclampsia risk: A meta-analysis.

BACKGROUND: Preeclampsia is a serious medical condition that significantly affects expectant mothers. Growing research showed an inconsistent association between TNF-alfa rs1800629 polymorphism and preeclampsia. The current meta-analysis was aimed at examining the potential impact of rs1800629 variant on preeclampsia. METHODS: The Cochrane Library, Google Scholar, PubMed, EMBASE, Web of Science, and other databases were searched extensively to locate and select articles up to October 30, 2023. The PRISMA 2020 recommendations were followed to perform this study. Data analysis was done by using Comprehensive Meta analysis (v 3). RESULTS: We have included 32 articles containing 35 studies with 3,883 patients and 5,821 controls for qualitative and quantitative data analysis. We found a strong relationship between rs1800629 variant with the increased preeclampsia risk in co-dominant model 1 (OR = 1.33, p = 0.019), co-dominant model 2 (OR = 1.43, p = 0.014), dominant model (OR = 1.25, p = 0.044), over-dominant model (OR = 1.31, p = 0.021), and allelic model (OR = 1.24, p = 0.018). This study also revealed a significantly higher risk among the Asian population in the dominant (OR = 2.31, p = 0.036) and allelic model (OR = 2.02, p = 0.028). For the Caucasian population, an increased association between the rs1800629 variant and preeclampsia risk was reported in co-dominant model 1 (OR = 1.37, p = 0.011), co-dominant model 2 (OR = 1.77, p = 0.007), dominant model (OR = 1.32, p = 0.030), recessive (OR = 1.50, p = 0.047), over-dominant (OR = 1.34, p = 0.009), and allelic model (OR = 1.32, p = 0.004). Though our study showed the protective link of the TNF-alfa polymorphism to the preeclampsia risk among the Black population, no significant outcomes were observed in any genetic models (p > 0.05). CONCLUSION: Overall, the present meta-analysis explored a consistent linkage of the TNF-alfa rs1800629 variant to the preeclampsia risk in different ethnic groups. Additional research is required to confirm the precise relationship between the rs1800629 variant and preeclampsia risk.

Link of BIN1, CLU, and IDE Gene Polymorphisms with the Susceptibility of Alzheimer's Disease: Evidence from a Meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder. The association of BIN1, CLU, and IDE genetic polymorphisms with AD risk have been evaluated overtimes that produced conflicting outcomes. OBJECTIVE: We performed this meta-analysis to investigate the contribution of BIN1 (rs744373 and rs7561528), CLU (rs11136000 and rs9331888), and IDE (rs1887922) polymorphisms to AD risk. METHODS: From a systemic literature search up to July 15, 2021, we included 25 studies with rs744373, 16 studies with rs7561528, 37 studies with rs11136000, 16 studies with rs9331888, and 4 studies with rs1887922. To analyze the correlation, we constructed seven genetic models that used odds ratio and 95% confidence intervals. We used RevMan 5.4 for meta-analysis. RESULTS: Our study suggests that BIN1 rs744373 is associated with a significantly increased risk of AD in five genetic models (OR>1). Again, CLU rs11136000 showed reduced association in all genetic models (OR<1). CLU rs9331888 revealed an increased association in two models (OR>1). The IDE rs1887922 showed significantly increased risk in four models (OR>1). From subgroup analysis, a significantly increased risk of AD was observed in Caucasians and Asians for BIN1 rs744373. Again, BIN1 rs7561528 showed a significantly enhanced risk of AD only in Caucasians. CLU rs11136000 showed significantly reduced risk in Caucasians but rs9331888 showed increased risk in the same ethnicity. CONCLUSION: Our meta-analysis confirms the association of BIN1 rs744373, CLU rs9331888, and IDE rs1887922 polymorphisms with an increased risk of AD, especially in Caucasians. Again, CLU rs11136000 is associated with reduced AD risk in the overall population and Caucasians.

Detection of association of IL1ß, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method.

BACKGROUND: Cervical cancer (CC) is the main cause of cancer-related deaths among women in developing countries. It is the second leading female malignancy in Bangladesh in terms of incidence and mortality. Our present study aimed to investigate the association of IL1ß (rs16944), IL4R (rs1801275), and IL6 (rs1800797) gene polymorphisms with the susceptibility of cervical cancer. MATERIALS AND METHODS: This case-control study was conducted on 252 cervical cancer patients and 228 healthy volunteers, using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: In the case of rs16944 polymorphism, GG genotype (OR = 2.10, 95%CI = 1.24-3.56), dominant model (OR = 1.71, 95% CI = 1.11-2.63), recessive model (OR = 1.54, 95% CI = 1.01-2.35), and G allele (OR = 1.30, 95% CI = 1.005-1.68) were significantly associated with increased cervical cancer risk. Among these, GG genotype and dominant model remained significant after the Bonferroni correction (p < 0.017). For rs1801275 polymorphism, GG genotype (OR = 2.66, 95% CI = 1.49-4.75), dominant model (OR = 1.49, 95% CI = 1.04-2.14), recessive model (OR = 2.45, 95% CI = 1.40-4.27), and G allele (OR = 1.59, 95% CI = 1.21-2.10) significantly elevated the risk of cervical cancer but significance did not exist for dominant model after the Bonferroni correction. rs1800797 variant showed significantly increased risk in all genetic models including, AG genotype (OR = 8.13, 95% CI = 5.27-12.55), AA genotype (OR = 9.86, 95% CI = 2.76-35.21), dominant model (OR = 8.25, 95% CI = 5.40-12.60), recessive model (OR = 4.41, 95% CI = 1.25-15.56), and A allele (OR = 4.99, 95% CI = 3.49-7.13) and the significances were consistent with the Bonferroni correction except recessive model. Haplotyping analysis indicates that GAA (p = 5.15x10-5) and GAG haplotypes (p = 4.72x10-9) significantly decreased the risk of CC, whereas AAA (p = 3.89x10-9), AAG (p = 0.0003), AGA (p = 3.98x10-5) and AGG haplotypes (p = 0.002) significantly increased the risk of CC. The IL1ß mRNA level was up-regulated, which was associated with poor prognosis in silico. CONCLUSION: Our results conclude that rs16944 (IL1ß), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.

Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women.

OBJECTIVE: Cervical cancer is one of the most destructive diseases among females worldwide, especially in developing countries. Interleukin-10 (IL10) is a multifunctional cytokine, and polymorphisms in the IL10 gene have been identified in multiple malignancies. However, no prior studies were conducted to determine the association of IL10 polymorphisms (rs1800872 and rs1800896) with cervical cancer patients in Bangladesh. METHODS: This case-control study was carried out on 240 cervical cancer patients and 204 healthy volunteers. Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR). RESULTS: In the case of rs1800872, CA and AA genotypes significantly increased the risk of cervical cancer (OR = 1.59, 95% CI = 1.01-2.49, p = 0.043; OR = 2.75, 95% CI = 1.53-4.93, p = 0.0007, respectively) but the significance did not exist for CA genotype after Bonferroni correction (p < 0.025). An increased risk was also observed for the dominant model, recessive model, and allele model (A vs. C) of rs1800872 (dominant model: OR = 1.83, 95% CI = 1.18-2.80, p = 0.006; recessive model: OR = 2.00, 95% CI = 1.22-3.29, p = 0.006; allele model: OR = 1.55, 95% CI = 1.19-2.03, p = 0.001) which remained significant after the correction of Bonferroni. For rs1800896, only GG genotype and recessive model showed increased risk for cervical cancer (GG vs. AA: OR = 3.48, 95% CI = 1.46-8.31, p = 0.005; recessive model: OR = 3.57, 95% CI = 1.52-8.38, p = 0.003). These associations were statistically significant, and the significance existed after Bonferroni correction. Haplotype analysis revealed that AA haplotype significantly increased the risk (OR = 1.56, p = 0.001) whereas, CA haplotype significantly lowered the risk (OR = 0.42, p = 2.42x10-8), and both rs1800872 and rs1800896 are strongly in linkage disequilibrium (D'=1, r2 = 0.333). Moreover, the IL10 mRNA level was found up-regulated in silico in cervical squamous cell carcinoma tissues compared to healthy tissues (p = 1.11x10-16). CONCLUSION: Our study suggests that rs1800872 and rs1800896 polymorphisms of IL10 gene are associated with cervical cancer in Bangladeshi females.

A Review on Current Repurposing Drugs for the Treatment of COVID-19: Reality and Challenges.

The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic with a high growth rate of confirmed cases. Therefore, therapeutic options are desperately urgent to fight with this damning virus. As it may take years to develop a specific therapy of COVID-19, it is urgent to emphasize the repurposing of drugs used for other conditions. This study reviewed the most common drugs for COVID-19 based on available online literature representing the latest in vitro clinical trial database, rational of use, adverse effects, potential toxicities, and US National Institute of Health (NIH) recommendation to use for COVID-19. Based on the preliminary data from clinical trials and considering the NIH and FDA recommendation, remdesivir and convalescent blood products are the most promising potential for COVID-19 treatment. The use of chloroquine, hydroxychloroquine, favipiravir, ivermectin, and colchicine might also be effective. However, furthermore, in vivo investigations are needed in detail individually and in combination for possible benefits in humans. Besides, tocilizumab might be deemed as adjunctive therapy for patients with cytokine release syndrome. However, lopinavir-ritonavir, anakinra, and sarilumab had not proven their clinical efficacy. Eventually, sarilumab has been withdrawn from sponsored clinical trials based on the preliminary data. Baricitinib and ruxolitinib have the additive immunosuppressive effect. Consequently, all of these drugs are being evaluated with further studies. In addition, drug-drug interaction and safety concerns must be taken into account before the administration of the recommended drugs.