Arterial involvement of lower limbs in peripheral artery disease - the difference between diabetics and non-diabetics.

OBJECTIVE: To detect peripheral artery disease in diabetic and non-diabetic individuals. METHODS: The case-control study was conducted from October 2018 to September 2019 at Ruth K.M. Pfau Civil Hospital, Karachi, and comprised diagnosed diabetic patients with random blood sugar ≥200mg/dl in group A, and healthy non-diabetic subjects in group B. Ankle brachial pressure index was measured and mean luminal diameters of lower limb arteries were compared using colour Doppler ultrasonography. Data was analysed using SPSS 21. RESULTS: Of the 82 subjects, 41(50%) were in each of the 2 groups. The sample had 42(51.2%) males and 30(48.8%) females with overall mean age of 53.9±5.07 years (range 44-60 years). There was significant difference in the ankle brachial pressure index values between the groups (p=0.004). There was also a significant difference in the mean luminal diameters of distal arteries (p=0.001), while there was no significant difference in proximal arteries (p>0.05). CONCLUSIONS: The diabetics were more prone to developing peripheral arterial disease than nondiabetics.

Etiology of Meningoencephalitis in children aged less than 5 years.

BACKGROUND: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. MATERIAL AND METHODS: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George's Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. RESULTS: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases. CONCLUSION: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.

Identification and Computational Analysis of Novel TYR and SLC45A2 Gene Mutations in Pakistani Families With Identical Non-syndromic Oculocutaneous Albinism.

Non-syndromic oculocutaneous albinism (nsOCA) is an inherited disorder of melanin biosynthesis with autosomal recessive mode of inheritance, presenting either hypopigmented or depigmented skin, hair, and eyes. It is genetically heterogeneous with seven loci (OCA1-OCA7) reported to date. In the present study, we have reported three consanguineous families (A, B, C) presenting identical nsOCA phenotypes. Sanger sequencing revealed a novel [NM_000372.5: c.826 T > C, p.(Cys276Arg)] and a recurrent variant [NM_000372.5: c.832C > T, p.(Arg278∗)] in tyrosinase (TYR) in families A and B, respectively. Microsatellite marker-based homozygosity mapping linked family C to OCA4. Sequence analysis identified a novel insertion variant (NM_016180.5: c.1331_1332insA) in the SLC45A2. Further, in silico mutagenesis and dynamic simulation approaches revealed that a novel Cys276Arg variant abolished the cysteine bridge and might contribute toward decreased stability of the TYR protein. Our study expands the mutation spectrum of the TYR and SLC45A2 genes and emphasizes that molecular investigations are essential for accurate disease diagnosis.

Role of the VDR Bsm I and Apa I polymorphisms in the risk of colorectal cancer in Kashmir.

OBJECTIVE: A case-control study aiming to evaluate the relationship between Bsm I and Apa I restriction fragment gene polymorphisms and colorectal cancer (CRC) was carried out in Kashmir, including a total of 368 subjects (180 cases and 188 controls). METHODS: DNA samples extracted from the blood of the subjects were analyzed for 3' untranslated region (3' UTR) Apa I and Bsm I polymorphisms using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). RESULTS: A statistically significant 2.7-fold increased risk was observed in individuals found homozygous for the presence of the 'b' allele, in comparison to subjects homozygous for the 'B' allele (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.49-4.86 (Bsm I)), and a statistically insignificant 2-fold increased risk was found among individuals with the 'aa' genotype, as compared to subjects with the 'AA' genotype (OR 2.017, 95% CI 0.86-4.7). Our study also yielded statistically significant results when the Apa I polymorphism was stratified by age (≤ 50 years) and dwelling area (rural area), and the Bsm I polymorphism by gender (male gender), suggesting a possible role of Apa I and Bsm I polymorphisms in the etiology of CRC in Kashmir. CONCLUSION: We conclude that Apa I and Bsm I single-nucleotide polymorphisms (SNPs) in the vitamin D receptor gene (VDR) might be associated with susceptibility to CRC among Kashmiris.

Association of a VDR gene polymorphism with risk of colorectal cancer in Kashmir.

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

ECRG1 and its relationship with esophageal cancer: a brief review.

Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC.

Polymorphisms in the 3'UTR of the human leptin gene and their role in hypertension.

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3' flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2 ± 5.12) and low (20.13 ± 1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3'UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p ≤ 0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3' flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.

Relation between IRF-1 gene and acute myelocytic leukemia in Kashmiri population.

The IRF-1 protein, a mammalian transcriptional factor encoded by a gene located in 5q23-q31, has antioncogenic properties. Involved in regulation of differentiation and proliferation, IRF-1 acts as a tumor suppressor gene and is inactivated by deletion of its one or more exons (exon skipping) in many hematological malignancies, including acute myelocytic leukemia (AML) and myelodysplastic syndromes (MDS). DNA samples, extracted from peripheral blood, taken from 50 Kashmiri AML subjects, were analysed using the polymerase chain reaction and compared with examples of age and gender matched healthy controls from the same population. Three different exon regions (2, 3 and 4) of the IRF-1 gene that were previously shown to be prone to deletion were selected for amplification and analysis. Deletion was observed in 31(62%) out of 50 AML patients (p=0.016). Exon 3 was most frequently deleted (58%), followed by exon 2 (28%), while exon 4 was least affected (12%), providing insights into critical roles in leukemogenesis. The number of deleted exons was variable, but single exon deletions were more frequent (30%). Of interest, IRF-1 gene deletions were not observed in 19 (38%) patients. In our study, the frequency of deletions of these three exons was slightly higher than in an Indian population (52%), but lower than in Sweden in Europe (95%). This study also explored the prevalence and clinical profile of IRF-1 deletions in AML patients. Adults had a significantly higher incidence than children (p=0.0168) and IRF-1 deletions were associated with low Hb (p< 0.0001), high TLC (p=0.0033) and a low platelet count (p=0.0076).

The ECRG1 290Arg/Gln polymorphism is related to risk of esophageal squamous cell carcinoma in Kashmir.

ECRG1 (esophageal cancer related gene 1) is a novel candidate member of the tumor suppressor gene family previously found to be down regulated in human esophageal cancer (ESCC). So far no evidence regarding the role of the ECRG1 gene in this cancer has been reported from the Kashmir valley, located on the border of the high risk 'esophageal cancer belt'. A case control study was therefore carried out with genomic DNA from 165 newly diagnosed ESCC patients (cases) and 200 control subjects. DNA was analyzed for ECRG1 polymorphisms by RFLP PCR, gel electrophoresis and direct sequencing. A statistically significantly increased risk of ESCC was found to be associated with the ECRG1 Arg/Gln and Gln/Gln genotype occurrence compared to the Arg/Arg genotype (odds ratio (OR) 1.698, 95% confidence interval (CI) 1.112-2.593); P= 0.0138) was observed. Statistically significant results were also obtained between the ECRG1 polymorphism and histophathological grade, smoking, dysphagia, low fruit/vegetable intake and salt tea consumption.