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Abstract Background Dental caries (DC) is a multifaceted oral condition influenced by genetic and environmental factors. Recent advancements in genotyping and sequencing technologies, such as Genome-Wide Association Studies (GWAS) have helped researchers to identify numerous genetic variants associated with DC, but their prevalence and significance across diverse global populations remain poorly understood as most of the studies were conducted in European populations, and very few were conducted in Asians specifically in Indians. Aim This study aimed to evaluate the genetic affinity of effect alleles associated with DC to understand the genetic relationship between global populations with respect to the Indian context. Methodology This present study used an empirical approach in which variants associated with DC susceptibility were selected. These variants were identified and annotated using the GWAS summary. The genetic affinity was evaluated using Fst. Results The effect of allele frequencies among different populations was examined, revealing variations in allele distribution. African populations exhibited higher frequencies of specific risk alleles, whereas East Asian and European populations displayed distinct profiles. South Asian populations showed a unique genetic cluster. Conclusion Our study emphasises the complex genetic landscape of DC and highlights the need for population-specific research as well as validation of GWAS-identified markers in Indians before defining them as established candidate genes.

Abstract Background Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups. Methodology The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. Result Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37–1.58. Conclusion This study identifies EFEMP1 as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.

Abstract Introduction Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations. Methods We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma. Participants wore accelerometers for 24-hours/day for seven days. Results Of 124 participants (44 mild, 80 difficult-to-treat), no between-group differences were observed in sleep-window, sleep-time, sleep efficiency or wake time. Sleep-onset time was ~ 40 min later in the difficult-to-treat group (p = 0.019). Discussion Broadly, we observed no difference in accelerometer-derived sleep-metrics between mild and difficult-to-treat asthma. This is the largest analysis of accelerometer-derived sleep parameters in asthma and the first comparing groups by asthma severity. Sleep-onset initiation may be delayed in difficult-to-treat asthma but a dedicated study is needed to confirm.

Abstract Background Difficult-to-control asthma associated with elevated body mass index (BMI) is challenging with limited treatment options. The effects of pulmonary rehabilitation (PR) in this population are uncertain. Methods This is a randomised controlled trial of an eight-week asthma-tailored PR programme versus usual care (UC) in participants with difficult-to-control asthma and BMI ≥ 25 kg/m2. PR comprised two hours of education and supervised exercise per week, with encouragement for two individual exercise sessions. Primary outcome was difference in change in Asthma Quality of Life Questionnaire (AQLQ) in PR versus UC groups between visits. Secondary outcomes included difference in change in Asthma Control Questionnaire-6 (ACQ6), and a responder analysis comparing proportion reaching minimum clinically important difference for AQLQ and ACQ6. Results 95 participants were randomised 1:1 to PR or UC. Median age was 54 years, 60% were female and median BMI was 33.8 kg/m2. Mean (SD) AQLQ was 3.9 (+/-1.2) and median (IQR) ACQ6 2.8(1.8–3.6). 77 participants attended a second visit and had results analysed. Median (IQR) change in AQLQ was not significantly different: 0.3 (− 0.2 to 0.6) in PR and − 0.1 (− 0.5 to 0.4) in UC, p = 0.139. Mean change in ACQ6 was significantly different: − 0.4 (95% CI − 0.6 to − 0.2) in PR and 0 (− 0.3 to + 0.3) in UC, p = 0.015, but below minimum clinically important difference. In ACQ6 responder analysis, minimum clinically important difference was reached by 18 PR participants (54.5%) versus 10 UC (22.7%), p = 0.009. Dropout rate was 31% between visits in PR group, and time to completion was significantly prolonged in PR group at 94 (70–107) days versus 63 (56–73) in UC, p

Abstract Background Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. Methods SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. Results The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08–2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136–5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123–0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46–0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. Conclusion It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Abstract Background MassARRAY (Agena Bioscience™) combines competitive PCR with MALDI-TOF mass spectrometry (MS) analysis that gives highly accurate, sensitive, and high-throughput methods for the quantitative analysis of variation of gene expression in multiple samples. SNPs (Single Nucleotide Polymorphisms) have a very high potential of discovering disease-gene relationships. SNP-genotyping through MassARRAY is not only a cost-effective genotyping method but also provides a platform to validate variants observed through a high-throughput Next-generation sequencing (NGS). Methods In the present study, we have incorporated the use of matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) as a tool for differentiating genotypes based on the mass of variant. We have performed multiplex PCR and genotyped 12 SNPs in 758 samples (166 cases and 592 controls). The 12 studied SNPs were chosen with a rationale for their association with multiple cancers in literature. Results This is the first study to explore these SNPs with esophageal cancer within the J&K population. Out of 12 SNPs, two SNPs rs12190287 of TCF21 and rs10046 of CYP19A1 were significantly associated with esophageal cancer with Odds Ratio (OR) 1.412 (1.09–1.8 at 95% CI, p = 0.008) and 1.54 (1.21–2.072 at 95% CI, p = 0.0007) within the population of Jammu and Kashmir. Conclusion We explored 12 SNPs that were found to be associated with multiple cancers in literature with esophageal cancer within the population of J&K. This is the first study to find the relation of these SNPs with ESCC within the studied population. This study explores the relation of genetic and environmental factors with the ESCC susceptibility.

Abstract Background Narrow genetic base, complex allo-tetraploid genome and presence of repetitive elements have led the discovery of single nucleotide polymorphisms (SNPs) in Brassica juncea (AABB; 2n = 4x = 36) at a slower pace. Double digest RAD (ddRAD) - a genome complexity reduction technique followed by NGS was used to generate a total of 23 million paired-end reads from three genotypes each of Indian (Pusa Tarak, RSPR-01 and Urvashi) and Exotic (Donskaja IV, Zem 1 and EC287711) genepools. Results Sequence data analysis led to the identification of 10,399 SNPs in six genotypes at a read depth of 10x coverage among the genotypes of two genepools. A total of 44 hyper-variable regions (nucleotide variation hotspots) were also found in the genome, of which 93% were found to be a part of coding genes/regions. The functionality of the identified SNPs was estimated by genotyping a subset of SNPs on MassARRAY® platform among a diverse set of B. juncea genotypes. SNP genotyping-based genetic diversity and population studies placed the genotypes into two distinct clusters based mostly on the place of origin. The genotypes were also characterized for six morphological traits, analysis of which revealed a significant difference in the mean values between Indian and Exotic genepools for six traits. The association analysis for six traits identified a total of 45 significant marker-trait associations on 11 chromosomes of A- and B- group of progenitor genomes. Conclusions Despite narrow diversity, the ddRAD sequencing was able to identify large number of nucleotide polymorphisms between the two genepools. Association analysis led to the identification of common SNPs/genomic regions associated between flowering and maturity traits, thereby underscoring the possible role of common chromosomal regions-harboring genes controlling flowering and maturity in Brassica juncea.

Abstract Background Telomere genetics has recently been emerged as an important field in molecular oncology. Various genome-wide association studies in different population groups have revealed that polymorphisms in Telomere maintenance gene (TERT) gene located on 5p15.33 is associated with susceptibility to leukemia and lung cancer risk. However, association of TERT with leukemia and lung cancer risk in north Indian population groups is still unknown. This study observed the association between genetic variant rs2853677 of TERT and leukemia and lung cancer in the state of Jammu and Kashmir, India. Methods A total of 781 subjects, out of which 381 cases (203 leukemic patients and 178 non-small cell lung cancer patients NSCLC) and 400 healthy controls were recruited for the study. Genetic variant rs2853677of TERT was detected using the real-time and Taqman Chemistry. Hardy-Weinberg Equilibrium was assessed using the chi square test. The allele and genotype- specific risks were estimated as odds ratio with 95% confidence interval. Results We observed that variant rs2853677 was strongly associated with lung cancer and leukemia risk with an odds ratio (OR) =1.8 (1.03–3.2 at 95% CI); p value (adjusted) = 0.03; odds ratio (OR) =2.9 (1.4–5.5.at 95% CI); p value (adjusted) = 0.002, respectively. Conclusion The results of this study suggested that rs2853677 of TERT signifies association in multiple cancers and suggests that it can become potential marker for diagnosis of non-small cell lung cancer and leukemia. The study will provide an insight in understanding the genetic etiology and highlights the role of telomere-associated pathways in non-small cell lung cancer and leukemia. However, it would be quite interesting to explore the contribution of this variant in other cancers as well.

Abstract Background Adverse effects of antileishmanial drugs can affect patients’ quality of life and adherence to therapy for visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). In Bangladesh, there are 26 treatment centers that manage leishmaniasis cases coming from 100 endemic upazilas (subdistricts) of 26 districts (these include VL, PKDL, treatment failure, and relapse VL and cutaneous leishmaniasis cases). This study aimed to investigate the feasibility of using focused pharmacovigilance for VL (VLPV) in Bangladesh’s National Kala-azar Elimination Programme for the early detection and prevention of expected and unexpected adverse drug reactions (ADRs). Methods This activity has been going on since December 2014. Activity area includes secondary public hospital or Upazila health complex (UHC) in hundred sub districts and Surya Kanta Kala-azar Research Center (SKKRC) in Mymensingh District, a specialized center for management of complicated VL and PKDL cases. Communicable Disease Control (CDC) of the Directorate General of Health Services (DGHS) assigned twenty five of hundred UHCs and SKKRC (total 26) as treatment centers depending on their suitable geographical location. This was implemented for better management of VL cases with Liposomal Amphotericin B (AmBisome®) to ensure patient convenience and proper utilization of this expensive donated drug. A VLPV expert committee and a UHC VLPV team were established, an operational manual and pharmacovigilance report forms were developed, training and refresher training of health personnel took place at UHCs and at the central level, collected information such as patient data including demographics, treatment history and response, adverse events were analyzed. This report includes information for the period from December 2014 to December 2016. Results From December 2014 to December 2016, 1327 leishmaniasis patients were treated and 1066 (80%) were available for VLPV. Out of these, 57, 33, 9, and 1% were new VL, PKDL, VL relapse, and other cases, respectively. Liposomal amphotericin B was mostly used (82%) for case management, followed by miltefosine (20%) and paromomycin (3%). Out of the 1066 patients, 26% experienced ADRs. The most frequent ADR was fever (17%, 176/1066), followed by vomiting (5%, 51/1066). Thirteen serious adverse events (SAEs) (eight deaths and five unexpected SAEs) were observed. The expert committee assessed that three of the deaths and all unexpected SAEs were possibly related to treatment. Out of the five unexpected SAEs, four were miltefosine-induced ophthalmic complications and the other was an AmBisome®-induced avascular necrosis of the nasal alae. The Directorate General of the Drug Administration entered the ADRs into the World Health Organization Uppsala Monitoring Centre (WHO-UMC) VigiFlow database. Conclusions This study found that VLPV through NKEP is feasible and should be continued as a routine activity into the public health system of Bangladesh to ensure patient safety against anti-leishmanial drugs.