Contribution of laboratory medicine and emerging technologies to cardiovascular risk reduction via exposome analysis: an opinion of the IFCC Division on Emerging Technologies.

This opinion article highlights the critical role of laboratory medicine and emerging technologies in cardiovascular risk reduction through exposome analysis. The exposome encompasses all external and internal exposures an individual faces throughout their life, influencing the onset and progression of cardiovascular diseases (CVD). Integrating exposome data with genetic information allows for a comprehensive understanding of the multifactorial causes of CVD, facilitating targeted preventive interventions.

Key methodological challenges in detecting circulating miRNAs in different biofluids.

The technological advancement in diagnostic techniques has immensely improved the capability of predicting disease progression. Yet, there is a great interest in developing newer biomarkers that can enhance disease risk prediction thereby minimising the associated morbidity and mortality. Circulating miRNAs, a non-coding RNA molecule, are critical regulators in the pathophysiology of various complex multifactorial diseases.

Targeted exome sequencing in South Indian patients with Familial hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD).

Objectives: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing.

Methods: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC).

Shortcomings on genetic testing of Familial hypercholesterolemia (FH) in India: Can we collaborate to establish Indian FH registry?

Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that affects ∼1 in 250-500 individuals globally. The only prevalence study in India shows FH in 15% of patients with premature CAD in North Indians. There are only 6 genetic studies in India of the total mutations, 32% are LDLR mutations, 4% are ApoB, 2% are PCSK9 mutations and the mutational spectrum for 37% is unknown.

Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India.

Familial Hypercholesterolemia (FH) is an autosomal, dominant, inherited disorder characterized by severely elevated LDL-cholesterol (LDL-C) levels with high risk for Coronary Artery Disease (CAD). There are limited genetic studies especially on genes other than Low Density Lipoprotein receptor (LDLR) conducted in Indian population. Thus, our aim was to screen the entire Proprotein Convertase Subtilisin/Kexin type 9 gene (PCSK9) gene & hotspot exons 3, 4 and 9 of LDLR gene in FH cases and controls.

Association of Genetic Variants with Hyperhomocysteinemia in Indian Patients with Thrombosis.

Hyperhomocysteinemia known to be associated with increased thrombotic tendency has been considered as a risk factor for coronary artery disease, atherosclerosis, venous thrombosis, and stroke. There are three main genes MTHFR, cystathionine beta-synthase (CBS) and methionine synthase (MS) and it's genetic variant that are known to influence the homocysteine metabolism leading to hyperhomocysteinemia. There is scarcity of Indian data on hyperhomocysteinemia and genetics variants in patients with thrombosis.

Reference intervals for 33 biochemical analytes in healthy Indian population: C-RIDL IFCC initiative.

Background In 2011, the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) initiated a worldwide multicenter study on references values facilitating the implementation of country-specific reference intervals (RIs). There has been no well-designed RI study in India. This study aims to derive RIs for 33 major biochemical analytes in carefully selected healthy Indians as defined in C-RIDL protocol.

Circulating miRNA-33: a potential biomarker in patients with coronary artery disease.

Background: Circulating microRNAs (miRNA) are present in body fluids in stable, cell-free form. Likewise, these miRNAs can be identified in various stages of coronary artery disease (CAD) such as inflammation, endothelial dysfunction, proliferation and atherosclerosis among others. miRNA expression levels can be identified.

Preemptive NUDT15 genotyping: redefining the management of patients with thiopurine-induced toxicity.

Background: Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy.

A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

Objectives: The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world.

Methods: As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry.

An in-house multilocus SNP genotyping assay for evaluation of complex genetic diseases.

Background: With an increase in the discovery of newer genetic loci/polymorphisms in complex multifactorial diseases, there is also an increased need for methods that can simultaneously genotype multiple loci in a cost-effective manner. Using coronary artery disease (CAD) as a model, the study aimed to develop an in-house multilocus assay for simultaneous detection of 17 genetic variants in 11 genes implicated in CAD.

Methods: A multiplex polymerase chain reaction (PCR)-based reverse line blot hybridization (MPCR-RLBH) approach was used, where each DNA sample was amplified using two separate MPCRs, and the alleles were genotyped using covalently immobilized, amino-linked sequence-specific oligonucleotide probes using an enhanced chemiluminescence system.

Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients.

Background And Aim: Interindividual variation seen in the thiopurine metabolism is attributed to the genetic variant in thiopurine methyltransferase (TPMT) gene leading to myelosuppression. In Asians, the thiopurine-induced toxicity is not completely explained by TPMT variants. Literature indicates that a newer genetic variant in nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene is associated with thiopurine intolerance.

Troponin T and Heart Type Fatty Acid Binding Protein (h-Fabp) as Biomarkers in Patients Presenting with Chest Pain.

Acute coronary syndrome (ACS) is a term for a range of clinical signs and symptoms suggestive of myocardial ischemia. It results in functional and structural changes and ultimately releasing protein from injured cardiomyocytes. These cardiac markers play a major role in diagnosis and prognosis of ACS.

Role of thrombomodulin gene in Indian population with coronary artery disease.

Context: Thrombomodulin (TM), a natural anticoagulant have been implicated in the pathogenesis of coronary artery disease (CAD) thus emphasizing its potential role as a biomarker.

Objectives: To investigate the role of the TM genetic variants and soluble TM (sTM) plasma levels in Indian population with CAD.

Materials And Methods: This case-control study involved genotyping of the entire TM gene and sTM levels estimation in 266 subjects.

Cardiovascular disease in India.

Cardiovascular disease (CVD) is one of the leading cause of mortality in India. It is estimated that 23.6 million CVD cases will be reported in subjects younger than 40 years of age by 2015, suggesting that young Indians are at higher cardiac risk.

Design of Allele Specific PCR for Rapid Detection of CYP3A5 (A6986G) and Mdr-1 (C3435T) Polymorphisms.

Single nucleotide polymorphisms in CYP3A5 (A6986G) and MDR-1 (C3435T) genes have been shown to be associated with the pharmacokinetics of tacrolimus in case of renal transplant recipients. Knowing these genotypes of the recipients before undergoing transplantation, is therefore essential for physicians to adjust the starting dose of tacrolimus in order to avoid drug induced nephrotoxicity. We have designed an allele specific PCR method for easier and rapid detection of these polymorphisms.

Prevalence of metabolic syndrome in urban India.

Background. Metabolic syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. Materials and Methods.

TPMT and DPD polymorphisms: Efficient screening method for Indian patients considering taking Thiopurine and 5-FU drugs.

Introduction: Development of DNA-based tests for TPMT/DPD polymorphisms can help clinicians and patients to make important decisions about cancer treatment. Also, due to lack of Indian data, we aimed at the development and validation of these tests in Indian patients.

Materials And Methods: Molecular assays were used for identifying TPMT/DPD variations; validated by DNA sequencing.