Unveiling hidden risks: pharmacogenetic insights from a cross-sectional study of statin therapy in the Indian population.

Background: Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).

Materials And Methods: Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.

Phenotypic Evolution in Fabry Disease: Our Experience in Indian Cohort.

The current study aimed to explore phenotypic evolution in Fabry disease according to demographics, genotype, specific enzyme activity and pathogenicity scores. We integrated clinical, biochemical, and genomic data of 88 Fabry cases (23 from our cohort, 65 from other published data on Indians) to achieve this objective. The affected cases showed profound impairment in the alpha galactosidase enzyme activity (0.

Elucidation of genetic determinants of dyslipidaemia using a global screening array for the early detection of coronary artery disease.

Dyslipidemia is a major risk factor for the development of coronary artery disease (CAD). Understanding the genetic determinants of dyslipidemia can provide valuable information on the pathogenesis of CAD and aid in the development of early detection strategies. In this study, we used a Global Screening Array (GSA) to elucidate the genetic factors associated with dyslipidemia and their potential role in the prediction of CAD.

The role of TLR7 agonists in modulating COVID-19 severity in subjects with loss-of-function TLR7 variants.

We investigate the mechanism associated with the severity of COVID-19 in men with TLR7 mutation. Men with loss-of-function (LOF) mutations in TLR7 had severe COVID-19. LOF mutations in TLR7 increased the risk of critical COVID by 16.

Application of machine learning tools and integrated OMICS for screening and diagnosis of inborn errors of metabolism.

Introduction: Tandem mass spectrometry (TMS) has emerged an important screening tool for various metabolic disorders in newborns. However, there is inherent risk of false positive outcomes. Objective To establish analyte-specific cutoffs in TMS by integrating metabolomics and genomics data to avoid false positivity and false negativity and improve its clinical utility.

Development of pharmacogenomic algorithm to optimize nateglinide dose for the treatment of type 2 diabetes mellitus.

Background: Nateglinide is a meglitinide used for the treatment of type 2 diabetes mellitus. Individual studies demonstrated the association of CYP2C9, SLCO1B1, and MTNR1B variants with the safety and efficacy of nateglinide. The current study aimed to develop a pharmacogenomic algorithm to optimize nateglinide therapy.

Molecular insights into the role of genetic determinants of congenital hypothyroidism.

In our previous studies, we have demonstrated the association of certain variants of the thyroid-stimulating hormone receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (TG) genes with congenital hypothyroidism. Herein, we explored the mechanistic basis for this association using different in silico tools. The mRNA 3'-untranslated region (3'-UTR) plays key roles in gene expression at the post-transcriptional level.

Tissue-specific DNase I footprint analysis confirms the association of Q470* variant with intellectual disability.

Intellectual disability (ID) is a neurodevelopmental disorder in which genetics play a key aetiological role. GATA zinc finger domain-containing 2B () gene encodes a zinc-finger protein transcriptional repressor which is a part of the methyl-CpG binding protein-1 complex. Pathogenic variants in this gene are linked to ID, dysmorphic features, and cognitive disability.

Pharmacogenetic determinants of warfarin in the Indian population.

Background: Several studies optimized the warfarin dose based on CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, CYP4F2 V433M. But, the information on the rare variants is lacking. In this study, we have explored the prevalence of common and rare pharmacogenetic determinants of warfarin and determined their damaging nature.

Influence of RFC1 c.80A>G Polymorphism on Methotrexate-Mediated Toxicity and Therapeutic Efficacy in Rheumatoid Arthritis: A Meta-analysis.

Background: Methotrexate (MTX) is an antirheumatic drug, transported by reduced folate carrier-1 (RFC1). The most common RFC1 gene variant, c.80 A>G (rs1051266) is ambiguously linked to adverse effects of MTX therapy in some rheumatoid arthritis (RA) patients.

Alpha synuclein (SNCA) rs7684318 variant contributes to Parkinson's disease risk by altering transcription factor binding related with Notch and Wnt signaling.

In view of inconsistencies in the association studies of alpha synuclein (SNCA) rs7684318 (chr4: 90655003 T > C) with Parkinson's disease (PD), we conducted a meta-analysis to establish the association of this variant with PD and examined changes in transcription factor binding. SNCA rs7684318 C-allele was identified as genetic risk factor for PD in fixed (OR: 1.53, 95 % CI: 1.

Pharmacogenetic profiling of dihydropyrimidine dehydrogenase (DPYD) variants in the Indian population.

Background: The present study aimed to delineate the pharmacologically relevant dihydropyrimidine dehydrogenase (DPYD) variants in the Indian population.

Methods: We screened 2000 Indian subjects for DPYD variants using the Infinium Global Screening Array (GSA) (Illumina Inc., San Diego, CA, USA).

Pharmacogenetic determinants of thiopurines in an Indian cohort.

Background: Several genetic variants of thiopurine metabolic pathway are associated with 6-thiopurine-mediated leucopenia. A population-based evaluation of these variants lays the foundation for Pharmacogenetic-guided thiopurine therapy.

Methods: A total of 2000 subjects were screened for the pharmacogenetic determinants using the infinium global screening array (GSA).

Newborn screening and single nucleotide variation profiling of TSHR, TPO, TG and DUOX2 candidate genes for congenital hypothyroidism.

High prevalence of congenital hypothyroidism (CH) among Indian newborns prompted us to establish population-specific reference ranges of TSH and to explore the contribution of the common genetic variants in TSHR, TPO, TG and DUOX2 genes towards CH. A total of 1144 newborns (593 males and 551 females) were screened for CH. SNV profiling (n = 22) spanning three candidate genes, i.

Probing the epigenetic signatures in subjects with coronary artery disease.

Depletion of S-adenosyl methionine and 5-methyltetrahydrofolate; and elevation of total plasma homocysteine were documented in CAD patients, which might modulate the gene-specific methylation status and alter their expression. In this study, we have aimed to delineate CAD-specific epigenetic signatures by investigating the methylation and expression of 11 candidate genes i.e.

The rs1991517 polymorphism is a genetic risk factor for congenital hypothyroidism.

The objective of the current study is to explore the association of thyroid-stimulating hormone receptor () rs1991517 polymorphism (c.2337 C > G, p.D727E) with congenital hypothyroidism (CH) through a case-control study followed by a meta-analysis.

Artificial neural network and bioavailability of the immunosuppression drug.

Purpose Of Review: The success of organ transplant is determined by number of demographic, clinical, immunological and genetic variables. Artificial intelligence tools, such as artificial neural networks (ANNs) or classification and regression trees (CART) can handle multiple independent variables and predict the dependent variables by deducing the complex nonlinear relationships between variables.

Recent Findings: In the last two decades, several researchers employed these tools to identify donor-recipient matching pairs, to optimize immunosuppressant doses, to predict allograft survival and to minimize adverse drug reactions.

Clinical and Molecular Diagnosis of Joubert Syndrome and Related Disorders.

Background: Joubert syndrome and related disorders are a group of ciliopathies characterized by mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia, and breathing abnormalities. Molar tooth sign in brain imaging is the hallmark for diagnosis. Joubert syndrome is a clinically and genetically heterogeneous disorder involving mutations in 35 ciliopathy-related genes.

Adaptive Neuro-Fuzzy Inference System-Based Exploration of the Interrelationships of 25-Hydroxyvitamin D, Calcium, Phosphorus with Parathyroid Hormone Production.

The rationale of the current study was to assess the prevalence of 25-hydroxyvitamin D (25-OHD) deficiency and hyperparathyroidism in South Indian population and to explore interrelationships of 25-OHD, Ca, P towards parathyroid hormone (PTH) production using adaptive neuro-fuzzy inference system (ANFIS). A total of 407 subjects (228 men 179 women) with the mean age 56.8 ± 14.

analysis of the structural and functional implications of R27H polymorphism.

In view of the documented association of solute carrier family 19 member 1 (SLC19A1) G80A (R27H) polymorphism with the risk for different types of cancers and systemic lupus erythematosus (SLE), we have reanalysed the case-control study on breast cancer to ascertain the conditions in which this polymorphic variant exerts the risk of breast cancer. Association statistics have revealed that this polymorphism exerts the risk for breast cancer under the conditions of low folate intake, and in the absence of well-documented protective polymorphism in cytosolic serine hydroxymethyltransferase. To substantiate this observation, we have developed a homology model of SLC19A1 using glycerol-3-phosphate transporter (d1pw4a) as a template where 73% of the residues were modelled at 90% confidence while 162 residues were modelled .