TGFß1 rs1800469 and SMAD4 rs10502913 polymorphisms and genetic susceptibility to colorectal cancer in Bangladeshi population.

BACKGROUND: Among Bangladeshi males and females, colorectal cancer is the fourth and fifth most prevalent cancer, respectively. Several studies have shown that the transforming growth factor beta 1 (TGFß1) gene and SMAD4 gene have a great impact on colorectal cancer. OBJECTIVE: The present study aimed to investigate whether TGFß1 rs1800469 and SMAD4 rs10502913 genetic polymorphisms are associated with susceptibility to colorectal cancer in the Bangladeshi population. METHODS AND MATERIALS: This case-control study was performed on 167 colorectal cancer patients and 162 healthy volunteers, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed for genotyping. RESULTS: In case of SMAD4 rs10502913 G > A polymorphism, the A allele reduced the colorectal cancer risk significantly (adjusted OR 0.35, 95% CI 0.23-0.52, p < 0.001) when compared to the G allele. It was also found that G/A and A/A genotypes of SMAD4 rs10502913 G > A polymorphism reduced the risk of colorectal cancer in comparison to the G/G genotype (G/A vs. G/G: adjusted OR 0.24, 95% CI 0.12-0.45, p < 0.001 and A/A vs. G/G: adjusted OR 0.06, 95% CI 0.02-0.21, p < 0.001). TGFß1 rs1800469 C > T polymorphism showed an elevated risk of developing colorectal cancer, although the results were not statistically significant. CONCLUSION: This study confirms the association of SMAD4 rs10502913 gene polymorphism with colorectal cancer susceptibility among the Bangladeshi population.

The link of ERCC2 rs13181 and ERCC4 rs2276466 polymorphisms with breast cancer in the Bangladeshi population.

BACKGROUND: Breast cancer (BC) is the most common disease in women and the leading cause of death from cancer globally. Epidemiological studies examined that nucleotide excision repair genes ERCC2 (rs13181) and ERCC4 (rs2276466) SNPs might increase cancer risk. Based on the previous investigation, this study was conducted to explore the correlation between these polymorphisms and BC susceptibility in Bangladeshi women. METHODS AND RESULTS: Between January 2019 and January 2020, 140 blood samples were collected from female patients histologically diagnosed with BC, and 111 female controls were recruited from non-cancer subjects. Genotyping was performed applying the PCR-RFLP method, and all statistical analyzes were conducted using SPSS, version 25.0. Comparison of characteristics and clinicopathological features between ERCC2 rs13181 and ERCC4 rs2276466 carriers and non-carriers showed no significant link with BC. Analysis of ERCC2 rs13181 with the risk of BC showed that the GG genotype and G allele carriers showed a fourfold and 1.78-fold higher risk (OR 4.00, P = 0.001 and OR 1.78, P = 0.002) that are statistically significant. In addition, the patients with combined TG+GG genotype revealed a 2.09-fold increased chance (OR 2.09, P = 0.020) BC development. Analysis of recessive model (GG vs. TT+TG) also depicted 2.74-times significantly higher risk (OR 2.74, P = 0.002). On the other hand, ERCC4 rs2276466 polymorphism did not show any significant association with BC (P > 0.05). CONCLUSIONS: Our findings show that ERCC2 rs13181 is linked to an elevated risk of BC. Our study also shows that ERCC4 rs2276466 polymorphism has no substantial risk of BC in the Bangladeshi population.

CHRNA5 rs16969968 and CHRNA3 rs578776 polymorphisms are associated with multiple nicotine dependence phenotypes in Bangladeshi smokers.

Background: A recent study has identified the role of CHRNA5-A3-B4 gene cluster variants rs16969968 and rs578776 of nicotinic acetylcholine receptors (nAChRs) on smoking status in Bengali ethnicity. The aim of the current study was to investigate whether these rs16969968-rs578776-rs11072768 single nucleotide polymorphisms (SNPs) of CHRNA5-A3-B4 gene cluster were associated with nicotine dependence (ND) and related phenotypes. Methods: The Fagerstrom Test for Nicotine Dependence (FTND) and Cigarette Dependence Scale (CDS-12) were used to assess the degree of ND, and genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on a cohort of 129 male smokers participating in a structured questionnaire-based survey. Results: Smokers with AA genotype of CHRNA5 rs16969968 SNP were at significantly increased risk of developing ND compared to its wild type variant with odds ratio (ORs) of 1.20 (FTND: 95% CI 0.25-5.37, p = 0.253) and 2.48 (CDS-12: 95% CI 0.46-13.26, p = 0.081), respectively. Conversely, smokers with AA genotype of CHRNA3 rs578776 variant had a strong protective effect against ND development (ORs = 0.27, 95% CI 0.09-0.80, p = 0.076). There was no such link reported in CHRNB4 rs11072768 variant carriers. Similarly, G-A/G-A diplotype of rs16969968_rs578776 variants was discovered to be a protective factor against ND. Moreover, demographic features such as age, occupation and dwelling status were found to be significantly associated with ND. Conclusion: Taken together, CHRNA5-A3-B4 gene cluster variants rs16969968 and rs578776 as well as specific demographic characteristics regulate ND and related smoking phenotypes in Bangladeshi male smokers. Further studies with large sample sizes are required to substantially validate the significance.

Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development.

Diabetes, a chronic physiological dysfunction affecting people of different age groups and severely impairs the harmony of peoples' normal life worldwide. Despite the availability of insulin preparations and several synthetic oral antidiabetic drugs, there is a crucial need for the discovery and development of novel antidiabetic drugs because of the development of resistance and side effects of those drugs in long-term use. On the contrary, plants or herbal sources are getting popular day by day to the scientists, researchers, and pharmaceutical companies all over the world to search for potential bioactive compound(s) for the discovery and development of targeted novel antidiabetic drugs that may control diabetes with the least unwanted effects of conventional antidiabetic drugs. In this review, we have presented the prospective candidates comprised of either isolated phytochemical(s) and/or extract(s) containing bioactive phytoconstituents which have been reported in several in vitro, in vivo, and clinical studies possessing noteworthy antidiabetic potential. The mode of actions, attributed to antidiabetic activities of the reported phytochemicals and/or plant extracts have also been described to focus on the prospective phytochemicals and phytosources for further studies in the discovery and development of novel antidiabetic therapeutics.

Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants influence smoking status in a Bangladeshi population.

BACKGROUND: Past studies have established the association of CHRNA5-A3-B4 gene cluster variants with various smoking behaviors in different ethnicities, yet no such study has been reported in Bengali ethnicity to date. METHODS: A case-control study with 129 smokers and 111 non-smokers was conducted and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method aimed to manifest the association of three SNPs in this gene cluster with smoking status (SS) in a Bangladeshi population. RESULTS: The non-synonymous CHRNA5 rs1s6969968 and 3'-UTR variant CHRNA3 rs578776 polymorphisms were found to have a strong association with SS. Carriers of polymorphic 'A' allele of rs16969968 showed 1.51-fold more risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.128); whereas, rs578776 polymorphic 'A' allele carriers showed 0.595-fold less risk of being smokers (adjusted OR = 1.51, 95% CI 0.88-2.57, p = 0.006). Comparing smokers and non-smokers, A/A mutant homozygous genotypes of rs578776 and rs16969968 variants pose 0.369-fold (95% CI 0.177-0.77, p = 0.008) and 3.3-fold (95% CI 0.66-16.46, p = 0.14) more risk for positive SS, respectively. No genotypic association for SS was found with intronic variant CHRNB4 rs11072768 (T/G; adjusted OR = 0.827, 95% CI 0.457-1.499, p = 0.532 and G/G; adjusted OR = 0.992, 95% CI 0.455-2.167, p = 0.985). Combination of rs16969968-positive/rs578776-negative polymorphic variants possesses the risk of positive SS in young adults. Furthermore, two new haplotypes (AAT and AAG) were identified in Bangladeshi population and GAG (OR = 0.45, 95% CI 0.25-0.8, p = 0.006) haplotype was found to be a protective factor for SS. CONCLUSION: Nicotinic acetylcholine gene cluster CHRNA5-A3-B4 variants rs16969968 and rs578776 are associated with SS in a Bangladeshi population. Large-scale studies are warranted to establish this genotype-phenotype correlation.

Prevalence of NPHS2 gene R229Q polymorphism in Bangladeshi children with nephrotic syndrome.

BACKGROUND: Limited and contradictory pharmacogenetic studies of NPHS2 gene R229Q polymorphism in nephrotic syndrome (NS) children of different ethnicities steered us to investigate the genotype frequency and associated risk of this polymorphism in Bangladeshi NS children. METHODS: A prospective case-control study was conducted which comprised a total of 142 children having nephrotic syndrome (NS), divided into 2 groups: case group consisted of 40 children with steroid-resistant nephrotic syndrome (SRNS), and control group involved 102 children with steroid-sensitive nephrotic syndrome (SSNS). Both were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for R229Q polymorphism. RESULTS: The results indicate the presence of R229Q polymorphism in 27.50% of SRNS and 12.75% of SSNS children. SRNS children possess 2.94-fold greater risk (p = 0.025) of carrying Arg/Gln genotype compared to SSNS children. Moreover, R229Q variant in SRNS children was observed as in a compound heterozygous form with p.Ala297Val located in exon 8. Age of onset (4-6 years) presents as a significant contributing factor (adjusted OR = 1.06; 95% CI = 1.023-1.094; p = 0.001) for SRNS susceptibility in Bangladeshi children. Contrarily, though the incidence of SRNS was higher in male children than female (80% vs 20%), gender remains to be a neutral factor (p = 0.257) in relation to SRNS susceptibility. CONCLUSION: Compound heterozygosity of NPHS2 p.R229Q gene variant with p.Ala297Val may cause pathogenic SRNS in Bangladeshi children. Large scale studies are warranted to establish the genotype-phenotype correlation. It is recommended to screen for p.R229Q first and, if positive, for p.Ala297Val in Bangladeshi SRNS children.