Genetic association of Interleukin-17A polymorphism in Bangladeshi patients with breast and cervical cancer: a case-control study with functional analysis.

BACKGROUND: Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer. METHODS: This case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases. RESULTS: From the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015). CONCLUSION: Our study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.

Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis.

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

The protective role of vitamin C in the management of COVID-19: A Review.

BACKGROUND: The outbreak of coronavirus infectious disease-2019 (COVID-19) is globally deemed a significant threat to human life. Researchers are searching for prevention strategies, mitigation interventions, and potential therapeutics that may reduce the infection's severity. One such means that is highly being talked in online and in social media is vitamin C. MAIN TEXT: Vitamin C is a robust antioxidant that boosts the immune system of the human body. It helps in normal neutrophil function, scavenging of oxidative species, regeneration of vitamin E, modulation of signaling pathways, activation of pro-inflammatory transcription factors, activation of the signaling cascade, regulation of inflammatory mediators, and phagocytosis and increases neutrophil motility to the site of infection. All of these immunological functions are required for the prevention of COVID-19 infection. CONCLUSION: Considering the role of vitamin C, it would be imperative to administrate vitamin C for the management of severe COVID-19. However, there is no specific clinical data available to confirm the use of vitamin C in the current pandemic.

Risk of type 2 diabetes mellitus and cardiovascular complications in KCNJ11, HHEX and SLC30A8 genetic polymorphisms carriers: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are two deadly diseases caused by the complex interaction of multiple genetic loci, lifestyle and environmental factors. Genome-wide association studies described hundreds of susceptibility loci for T2DM and T2DM-related CVD, but it remains uncertain due to geographic and ethnic variations. The objective of this study was to evaluate the associations of KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms with T2DM and related CVD. METHODS: Genotyping of all three polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on 250 T2DM cases and 246 healthy controls. Both descriptive and inferential statistical methods were applied using MedCalc and IBM SPSS software programs for statistical analyses. RESULTS: A significantly increased association of KCNJ11 rs5219 (p<0.05) with T2DM was found in dominant, recessive, heterozygote, homozygote, and allele model (aOR = 2.23, 2.03, 1.90, 3.09, and 1.80, respectively). For SLC30A8 rs13266634, only dominant, heterozygote, and allele model (aOR = 3.37, 3.59, and 1.79, respectively) showed significantly increased association with T2DM. SNP rs1111875 (HHEX) also revealed 2.08, 4.18, 5.93, and 2.08-times significant association in dominant, recessive, homozygote, and allele models. Besides, a significantly reduced correlation of KCNJ11 rs5219 was found with T2DM-related CVD in the recessive and allele model (aOR = 0.40 and 0.65, respectively). Again, a significant difference was observed between T2DM-related CVD and non-CVD patients in terms of gender distribution, fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and triglycerides (TG). CONCLUSIONS: Our investigation indicates that KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms are associated with T2DM. Moreover, KCNJ11 rs5219 polymorphism is correlated with the risk of T2DM-related CVD.

Severe acute respiratory syndrome coronavirus 2 invasion in the central nervous system: a host-virus deadlock.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) devastation on the central nervous system (CNS) is ascertained by the present clinical findings and the noticeable signs and symptoms. The CNS involvement of the virus is not trivial; although the brain has highly protective systems, the virus has ways to breach them with a destructive potential. For successful entry of the virus, different possible routes with favorable mechanisms are used. The SARS-CoV-2 invasion induces a mechanism of both the innate and adaptive immune response to control virus replication and removal from the CNS tissues. The cytokine storm and autoimmune response during the immunological events result in demyelination, damage of resident cells and neurons, cerebrovascular thrombosis, and dysregulation of neuro signaling pathways. Furthermore, hypoxia and toxemia accelerate the neurological destruction process. The acute attributions on psychology due to inflammation is a hallmark of CNS involved pathogenesis; nevertheless, the productivity, durability, and longevity of virus-specific lymphocytes are the vital indicators for complete removal of viral antigen and in combat against reinfection of the CNS. Keywords: CNS invasion; immune response; cytokine storm; demyelination; mental status.

CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by communication deficits, impaired social interactions, repetitive and stereotyped behaviors with restricted interests, and connected with the interaction between environmental factors and genetic vulnerability. CNTNAP2 gene has been extensively investigated for ASD and related neurodevelopment diseases. However, previous studies have resulted in an inconsistent outcome. Based on this fact, we conducted a case-control study followed by a meta-analysis to investigate the association of rs7794745 and rs2710102 polymorphisms with ASD. A total of 216 autistic children and 240 healthy volunteers were recruited, and genotyping was performed using the PCR-RFLP method. We observed that SNP rs7794745 revealed a significantly (p < 0.05) increased association with the development of ASD in children in all genetic models. No significant association was found for rs2710102 with ASD. Besides, rs2710102 exhibited a significant association with language impairment in TC genotype, C allele, and dominant model. From the meta-analysis of both SNPs, we found a significant association in codominant 1, 2, and the dominant model of rs2710102 and codominant 1 and dominant model of rs7794745 with ASD. Our case-control study suggests that rs7794745 polymorphism is associated with ASD, while rs2710102 is correlated with language impairment. Moreover, meta-analysis results indicated the association between both rs7794745 and rs2710102 polymorphisms and ASD.

Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.

OBJECTIVE: Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case-control study to investigate the association of INSIG2 rs6726538 (A; T), HLA-DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer. METHODS: The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method for genotyping. RESULTS: The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19-4.97, p < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87-19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61-5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20-4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09-0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31-0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32-0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40-0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45-10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06-2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34-2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09-0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883. CONCLUSION: Our study concludes that INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population.