Apolipoprotein E Polymorphism and Alzheimer’s Risk in Kashmiri Population

Background: Although the cause of Alzheimer's disease is unknown, most experts feel that the disease is caused by a combination of circumstances rather than a single cause. Age, gene polymorphism, diabetes, and other conditions are all risk factors for Alzheimer's disease. Given the importance of gene polymorphism in different diseases, we intended to find out the association of APOE gene polymorphism with Alzheimer's risk in the Kashmiri population. Method: Out of 300 patients who were referred to the memory clinic of the hospital, to evaluate the probable relation of APOE gene variation in Alzheimer's disease, we conducted the study on 59 clinically confirmed Alzheimer's patients and 52 age and ethnicity-matched healthy controls found in a community survey. Results: Our data revealed a statistically significant association of ε4 variant genotype of the APOE gene with AD susceptibility in the Kashmiri population. Conclusions: The current study's findings provided insight into the role of APOE polymorphisms in Alzheimer's disease susceptibility. The identified susceptibility variant may become a marker genotype for AD.

Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer

AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of ARID1A and elevated mRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.

STUDY OF FINGERPRINT PATTERN IN KASHMIRI POPULATION

Background: Dactylography/Dactyloscopy/Dermatoglyphics is the study of fingerprints as a method of identification.Fingerprint is an easily available,accurate and authentic method of identification.Importance of fingerprints is of immense use in forensic,and criminal application.Nowadays the subject is also developing importance in various other field as well.A Aim:To identify the fingerprint pattern and its relation with gender in kashmiri population. Material and Method: A cross sectional study was done in the government chest disease hospital.The subjects were the staff of the department belonging to various regions and districts of kashmir.The subjects were asked to press their fingers on the stamp pad and then transfered to the paper. Result: Loops were the most common pattern found followed by whorls and arches.Loops was found in 53.8%,whorls in 39.5% and arches in 6.7%.In gender wise distribution a higher percentage of loops was found in females and whorls in males. Conclusion: In the current research work different types of fingerprint patterns were found. Fingerprint is an easily available and effective method of identification of a person. This study will prove helpful to experts in solving criminal cases, identifying missing persons or in case of a disaster.

DISTRIBUTION OF ANATOMIC VARIATIONS OF THE NOSE AND PARANASAL SINUSES IN KASHMIRI POPULATION BY COMPUTED TOMOGRAPHY SCAN ANALYSIS.

Background: Knowledge of anatomy constitutes an integral part of the total management of patients with sinonasal diseases. The aim of this study was to obtain the prevalence of sinonasal anatomic variations in the Kashmiri population and to understand their importance and impact on the disease process, as well as their influence on surgical management and outcome. Materials and Methods: This study is a prospective review of retrospectively performed normal computed tomography (CT) scans of the nose and paranasal sinuses in the adult Kashmiri population at SMHS Hospital. The scans were reviewed by two independent observers. Results: The most common anatomic variation after excluding agger nasi cells were pneumatized Crista Galli, which was seen in 69% of the scans. However, the least common variation seen in this series was Pneumatized inferior turbinate, which was encountered in 1.1 % of the cases. Conclusion: A wide range of regional differences in the prevalence of each anatomic variation exists. Understanding the preoperative CT scan is substantially important because it is the roadmap for the sinus surgeon. Detection of anatomic variations is vital for surgical planning and the prevention of complications.

Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome

Background. Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. Methods. The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. Results. WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. Conclusion. Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.