Association of vitamin D receptor gene polymorphisms in North Indian children with asthma: a case-control study.

Asthma is a complex genetic disease. Vitamin D and vitamin D receptor (VDR) gene polymorphisms are involved in asthma pathogenesis. However, accurate inflammatory mechanisms and their role in VDR gene polymorphisms are unclear. The objective of this study was to investigate the association of VDR gene polymorphisms, ApaI, FokI, TaqI, and BsmI with asthma as compared to controls. Children (age 5-15 years) with a history of respiratory symptoms (wheeze, shortness of breath and chest tightness) were recruited as cases. Age matched children admitted with central nervous system disorders (encephalitis/seizures) without any respiratory complaints were recruited as controls after parental consent. Children with a clinical diagnosis of cystic fibrosis, congenital heart disease and whose parents did not consent for participation in the study were excluded. VDR gene polymorphisms were genotyped using PCR-RFLP method. One hundred and sixty asthmatics and one hundred controls were enrolled in this study. Mean age of the cases was 103.29±32.7 months and controls 94.24±30.52 months. Children with heterozygous (AC) genotype [OR=1.83, 95% CI=1.01-3.32, p=0.046] of ApaI polymorphism were found to be associated with the risk of asthma. Our findings suggest that ApaI polymorphism of VDR gene may contribute to asthma susceptibility among children.

Modeling the hydroxylation of estragole via human liver cytochrome P450.

Natural compounds derived from plants are generally regarded safe and devoid of adverse effects. However, there are individual ingredients that possess toxic, genotoxic, and carcinogenic activities. These compounds when exposed at specific level become hazardous to health. Estragole (1-allyl-4-methoxybenzene) is a common component of spice plants. Its toxicity gets activated with the hydroxylation at benzylic carbon (C1') position by P450 enzymes present in the human liver. The present study grounds to explore the reaction mechanism of conversion of estragole to hydroxylated metabolite using computational methodology. Density functional theory (DFT)-based calculations were employed to explore the cytochrome P450-catalyzed mechanism at C1 position aliphatic hydroxylation of estragole. Overall reaction energy profile, electronic configuration, and 3D structure of all intermediates, transition states, and product complexes formed during the reaction along with their free energies were tried to be investigated.

Association of Interleukin-1ß-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia.

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1ß) gene polymorphisms, (IL-1ß-31, IL-1ß-511 and IL-1ß-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR-RFLP) method and IL-1ß plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1ß was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1ß-3954 genotype. IL-1ß-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1ß gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1ß gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.

Role of VDR gene polymorphisms with community acquired pneumonia in North Indian children: a case-control study.

Community-acquired pneumonia (CAP) is a leading cause of death in children under five years of age globally. Currently, the vitamin D receptor (VDR) gene is an emerging factor that regulates inflammatory pathways that may alter the response to infections and possibly modify the outcome of CAP. The objective of this study was to investigate the association of VDR gene polymorphisms ApaI, FokI, TaqI, BsmI with CAP in children aged 2-59 months. Hospitalized children aged (2-59 months) with WHO-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital within one week of the recruitment of the case. Children with a clinical diagnosis of cystic fibrosis and congenital heart disease were excluded. Four VDR gene polymorphisms, ApaI, FokI, TaqI, BsmI were genotyped by using PCR-RFLP. From Oct-2016 to Oct-2019, 160 cases (34.37% females) and 160 controls (47.5% females) were recruited. Mean age of the cases was 26.30±23.10 months and controls 25.93±15.99 months. In FokI (rs2228570 polymorphism, heterozygous genotype (CT) [OR=2.06, 95% CI=1.25-3.39, P=0.00] and mutant allele (T) [OR=1.45, 95% CI=1.06-2.00, P=0.02] were found to be associated with the risk of CAP. In VDR gene, FokI polymorphism predisposes to CAP in Indian children.

Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community-acquired pneumonia in children: A hospital-based study in India.

BACKGROUND: High morbidity and mortality due to community-acquired pneumonia (CAP) is seen in children under 5 years of age in India. Besides identified risk factors for CAP, there may be a phenotype-genotype association with cytokines, resulting in enhanced inflammatory response resulting in the adverse outcome (AO), namely complications and death. AIM: To assess the association of IL1RA gene polymorphism on serum levels of IL1RA and with AO in children under 5 years of age hospitalized with WHO-defined severe CAP. METHOD: A prospective cohort study with nested case-control design conducted in a tertiary care teaching hospital after obtaining institutional ethical approval. Included were children between 2 and 59 months of age hospitalized with WHO-defined severe CAP with consistent radiological abnormalities. Excluded were those with suspected or proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA test to detect serum levels of IL1RA. RESULTS: From 2014 to 2016, of 420 screened cases, 350 were eligible and included, of which 132 (37.7%) had no complication and 218 (62.3%) had AO, which included complications like empyema, pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p 0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was statistically significantly elevated in CAP with AO (2.55 ± 1.44) versus uncomplicated (0.87 ± 0.52) (P < 0.0001). CONCLUSION: In IL1RA gene, A1A1 genotype was associated with lower risk and A2A2 genotype with increased the risk of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating possibly enhanced inflammatory response resulting in AO of CAP.

Role of salivary biomarkers in early detection of oral squamous cell carcinoma.

INTRODUCTION: Oral cancer is prevalent worldwide and is a common cause of morbidity and mortality. Despite advances in treatment, the survival of patients with oral cancer has not significantly improved over the past several decades owing to late detection and treatment failures. The present study was undertaken with an objective to explore the role of salivary CYFRA 21-1, CA 19-9, lactate dehydrogenase (LDH), total proteins, and amylase as biochemical markers of oral squamous cell carcinoma (OSCC) and premalignant lesions (PML). MATERIALS AND METHODS: This was a cross-sectional study for diagnostic test evaluation conducted in KGMC Lucknow, between 2010 and 2011. The study population comprised newly diagnosed cases of OSCC (Group I) and PML of oral cavity (Group II) who had not yet received any definitive therapy along with age- and gender-matched healthy controls (Group III). Unstimulated whole saliva was collected from the cases and controls. CYFRA 21-1 and CA19-9 were estimated by ELISA while LDH, total proteins, and amylase were evaluated as per standard kit method. RESULTS: Both OSCC and PML group showed increased salivary CYFRA 21-1, LDH, and total protein concentrations as compared to controls, but the increase in PML was significantly lower as compared to OSCC. A considerable decrease in concentration of amylase was seen in OSCC and PML as compared to control group. CONCLUSION: The outcome of this study suggests that concurrent analysis of salivary CYFRA 21-1, LDH, total protein, and amylase can be utilized for early detection of oral cancer.