Implications of lipoprotein (a) [Lp(a)] gene polymorphic sequence variations and its protein expression in venous thromboembolism (VTE).

Background: Venous thromboembolism (VTE) is a significant global health concern, with an annual incidence of approximately 1-2 per 1000 individuals. VTE is a major cause of morbidity and mortality worldwide, leading to substantial healthcare costs due to hospitalizations, long-term anticoagulation therapy, recurrent thrombotic events and the need for lifelong clinical management. The burden of VTE is particularly pronounced in aging populations, with incidence rates increasing exponentially after the age of 50.

Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

Background: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India).

Methods: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively.

Regulatory role of miR-125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses.

Objectives: Studies have investigated miR-125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3.

Methods: The present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR-125a was conducted by quantitative real-time PCR (qPCR).

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

Background: Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma.

Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.

Background: Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease.

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

Background: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC.

Method: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases.

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer.

Background: The polymorphic variations of human telomerase reverse transcriptase () gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of gene.

Materials And Methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of rs2736098 and rs2736100.

Implications of Decreased Expression of miR-125a with Respect to Its Variant Allele in the Pathogenesis of Recurrent Pregnancy Loss: A Study in a High Incidence Zone.

Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing.

Analysis of MNS16A VNTR polymorphic sequence variations of the gene and associated risk for development of bladder cancer.

Background: The MNS16A variable number tandem repeat (VNTR) polymorphism of the human telomerase reverse transcriptase () gene acts as a regulator of promoter activity and has been shown to have a role in the predisposition toward various cancers. The current study aimed to investigate the association between MNS16A VNTR alleles and genetic predisposition to bladder cancer in the Kashmir region of northern India.

Materials And Methods: A total of 130 patients with bladder cancer and 170 age- and gender-matched healthy controls were included in this study.

and rs156697 Polymorphism in Influence the Risk and Therapeutic Outcome of B-Acute Lymphoblastic Leukemia Patients.

Introduction: Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case-control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population.

Methods: A total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques.

Implications of VEGF gene sequence variations and its expression in recurrent pregnancy loss.

Research Question: What is the association between VEGF gene sequence variants and its mRNA expression in recurrent pregnancy loss (RPL)? Vascular endothelial growth factor (VEGF) has a prominent role in pregnancy and affects pregnancy outcome. The association of VEGF gene 1154G>A, 634G>C and 583C>T polymorphic variations with cases of RPL and full-term fertile women as controls was investigated.

Design: Two hundred women with RPL and 240 women healthy controls were included.

High incidences of chromosomal aberrations and Y chromosome micro-deletions as prominent causes for recurrent pregnancy losses in highly ethnic and consanguineous population.

Purpose: Recurrent Miscarriages (RM) commonly complicates the reproductive outcome where prominently chromosomal aberrations and molecular factors lead to recurrent miscarriages. We investigated couples with RM for cytogenetic abnormalities and Y chromosome microdeletions in males along with detection of aneuploidies de novo in the product of conception from a highly ethnic consanguineous population (Kashmir, North India) .

Study Design: Chromosomal analysis was done by Karyotyping on peripheral blood lymphocyte cultures and analyzed by Cytovision software Version 3.

Significant Implications of Gene Sequence Variations and Its Protein Expression in Bladder Cancer.

Apolipoprotein A1 () is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the genotypes of -75 G/A and +83 C/T in tandem with the protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and genotypes. The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex, and smoking status.

Association of -75G/A and +83C/T polymorphic variation with acute coronary syndrome patients in Kashmir (India).

Acute coronary syndrome (ACS) comes under the ambit of cardiovascular disease.APOA-1 gene plays a vital role in lipid metabolism and has been observed to have plausible role in ACS. This cross sectional case-control study was conducted to evaluate association between 1-75G/A(rs1799837), +83C/T (rs5069) genotypes and risk for ACS.

Influence of prominent immunomodulatory cytokines TNF-α308 G>A (rs1800629) and TGFβ1 G>C (rs1800471) sequence variations as an important contributing factor in etiopathogenesis of recurrent miscarriages in Kashmiri women (North India).

Aim: We aimed to evaluate the genetic variation of tumor necrosis factor-α (TNF-α) 308 G>A (rs1800629) and transforming growth factor (TGF) β1G>C (rs1800471) to confer risk in patients with recurrent miscarriage in highly consanguineous population of Kashmir (North India).

Methods: A total of 200 women who experienced two or more recurrent miscarriages (along with 100 spouses, 60 products of conception, and 240 healthy controls) with two or more full-term pregnancies were recruited from the same geographical region and evaluated by polymerase chain reaction-restriction fragment length polymorphism method.

Results: TNF-α 308 G>A variant genotype (AA) was significantly associated with recurrent miscarriage cases (2.

Favorable role of 1/2 mutations aided with promoter gene methylation in the outcome of patients with malignant glioma.

Aim: The implications of molecular biomarkers 1/2 mutations and gene promoter methylation were evaluated for prognostic outcome of glioma patients.

Materials & Methods: Glioma cases were analyzed for 1/2 mutations and promoter methylation by DNA sequencing and methylation-specific PCR, respectively.

Results: Mutations found in 1/2 genes totaled 63.

Glutathione S-transferase gene polymorphic sequence variations: Association with risk and response to Imatinib among Chronic Myeloid Leukemia patients of Kashmir.

Introduction: Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML.

Material And Methods: A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex-PCR and PCR-RFLP techniques.

Association of strong risk of hTERT gene polymorphic variants to malignant glioma and its prognostic implications with respect to different histological types and survival of glioma cases.

Background: Germline genetic variants of human telomerase reverse transcriptase (hTERT) are known to predispose for various malignancies, including glioma. The present study investigated genetic variation of hTERT T/G (rs2736100) and hTERT G/A (rs2736098) with respect to glioma risk.

Methods: Confirmed cases (n = 106) were tested against 210 cancer-free healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique for genotyping.

Influence of bcr-3 PML-RARα transcript on outcome in Acute Promyelocytic Leukemia patients of Kashmir treated with all-trans retinoic acid and/or arsenic tri-oxide.

Aims: Distinct types of PML-RARα hybrid transcripts viz bcr-1, bcr-2 and bcr-3 result from translocation between chromosomes 15 and 17 t(15;17) in Acute Promyelocytic Leukemia patients. We aimed to determine the frequencies of the PML-RARα transcripts and FLT3-ITD mutations in APL patients to evaluate their prognostic implications and also to analyze their impact on disease outcome.

Main Method: RT-PCR and Rq-PCR were adopted for transcript typing and quantitation of PML-RARα transcripts while FLT3-ITD was detected by PCR in APL patients.

Real-time quantitative PCR: a reliable molecular diagnostic and follow-up tool for 'minimal residual disease' assessment in chronic myeloid leukemia.

Molecular monitoring of BCR-ABL transcript levels by real-time quantitative PCR is increasingly being used to diagnose the disease and assess treatment response in patients with chronic myeloid leukemia (CML). This has become particularly relevant when residual levels of leukemia usually fall below the level of detection by cytogenetic analysis. Forty-two CML patients, including 18 males (42.

Prognostic Implication of BCR-ABL Fusion Transcript Variants in Chronic Myeloid Leukemia (CML) Treated with Imatinib. A First of Its Kind Study on CML Patients of Kashmir.

Background: The prognostic significance of the common BCR-ABL transcripts like e13a2 (b2a2) and e14a2 (b3a2) in Chronic myeloid leukemia (CML) has been reported from patients treated with different tyrosine kinase inhibitors but its impact on clinical response and overall survival remains still unexplored. The aim of this study was to evaluate the prognostic significance of different transcript types in a cohort of CML patients treated with imatinib. Methods: A total 42 confirmed cases of Chronic Myeloid Leukemia (CML) patients were recruited into our cohort study and a multiplex Reverse Transcriptase-Polymerase Chain Reaction technique (RT-PCR) was used to detect 3 main transcript types ‘e1a2’, ‘e13a2’, and ‘e14a2’ found in CML.

Significant Pattern of Promoter Hypermethylation of UNC5C Gene in Colorectal Cancer and Its Implication in Late Stage Disease.

Background:The development of Colorectal Cancer (CRC) is a complex multistep process involving an accumulation of multiple genetic and epigenetic alterations. Epigenetic modifications, particularly DNA methylation in selected gene are recognized as common molecular alterations in human tumors. Netrin-1 receptors are aberrantly methylated in primary colorectal cancer.

Concordant association validates MGMT methylation and protein expression as favorable prognostic factors in glioma patients on alkylating chemotherapy (Temozolomide).

O-methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC).