Adfar Yousuf

Role of TP53 Arg72Pro polymorphism in urinary bladder cancer predisposition and predictive impact of proline related genotype in advanced tumors in an ethnic Kashmiri population

Among various polymorphic variants of TP53 gene, codon 72 polymorphism (Arg72Pro) has been found to be associated with cancer susceptibility, but only few studies have investigated their effect on bladder cancer risk. A case-control study was conducted and we observed the genotype distribution of TP53 Arg72Pro SNP, to elucidate the possible role of this SNP as risk factor in urinary bladder cancer (UBC) development and to examine its correlation with the clinicopathologic variables of UBC cases. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we tested the genotype distribution of 108 bladder cancer patients in comparison with 138 cancer-free controls from the same geographical region. We observed significant differences between the control and bladder cancer patients with odds ratio = 2.9 and 95% confidence interval = 1.5-4.5 (P = 0.00001). Interestingly, the proline form was abundantly observed in advanced tumors (P < 0.05). We also found a significant association of the variant allele (GC+CC) with male subjects and ever smokers (P = 0.001). Thus, it is evident from our study that Arg72Pro SNP is implicated in bladder cancer, and that the rare, proline-related allele is connected with higher susceptibility to bladder cancer.

Study of TLR4 and IL-8 Gene Polymorphisms in H.pylori-Induced Inflammation in Gastric Cancer in an Ethnic Kashmiri Population

Background: TLRs play an essential role in the initial handling of H. pylori and determine the clinical outcomes that range from simple asymptomatic gastritis to peptic ulcer disease and gastric cancer. Asp299Gly and Thr399Ile polymorphisms in TLR4 have been associated with a variety of inflammatory and infectious conditions including gastric cancer. The T-251A polymorphism in the promoter region of IL-8 gene has been found to be associated with changing the in vitro levels of IL-8 production. IL-8 exhibits angiogenic activity and is responsible for tumor-associated angiogenesis in several cancers. Materials and methods: 130 gastric cancer patients and 200 healthy controls were included in this study. DNA extraction was followed by PCR detection of H. pylori infection, PCR-RFLP for the TLR 4 polymorphism and PCR-CTPP for IL-8 gene polymorphism. Results: The adjusted OR for gastric cancer risk was 1.15 (95% CI, 0.8357–1.3463); 1.39 (0.6964-2.781) and 1.43 (0.954–2.1515) for Asp299Gly, Thr399Ile and IL-8 T_251A respectively. Odds Ratio analysis showed CT genotype and AT and AA genotypes as risk factors for the development of gastric cancer. We found the Asp299Gly polymorphism carrier to be significantly associated (p value 0.03)with the development of tumours in the distal part of the stomach and Thr399Ile polymorphism to be significantly associated(p value 0.008) with the development of well-differentiated gastric adenocarcinoma.The IL-8 T-251A polymorphism was not found to be associated with any of the clinicopathological characteristics. Discussion: No correlation was found between the appearance of disease and HP infection or the presence of TLR4 and IL-8 gene polymorphisms and HP infection.

hs-CRP: A potential marker for hypertension in Kashmiri population

Hypertension is the most important public health problem in developing countries and one of the major risk factors for cardiovascular diseases, and it has been reported that hypertension is in part an inflammatory disorder and several workers have reported elevated levels of CRP in hypertensive individuals. The main aim of the present study was to evaluate the association between blood pressure and serum CRP levels across the range of blood pressure categories including prehypertension. A total of 104 patients and 63 control subjects were included in the present study. The level of CRP in the serum samples was estimated by a high sensitivity immunoturbidometric assay. Standard unpaired student’s ‘t’ test was used for comparison of hs-CRP levels between hypertensive patients and normotensive control subjects and between patient groups with different grades of hypertension and different durations of hypertensive histories. The mean serum hs-CRP level in hypertensive patients was 3.26 mg/L compared with 1.36 mg/L among normotensive control subjects (P<0.001). On comparison with normotensive control subjects, the hs-CRP levels vary significantly both with grades and duration of hypertension, with most significant difference found in patients with prehypertension (P<0.001), followed by Stage-I (P=0.01) and Stage-II(P=0.02) hypertensives. Significant difference in hs-CRP levels was also found in patients with shorter duration of hypertensive history (≤ 1year) when compared with those with ≥5 years of hypertensive history (P<0.01). Our study reveals a graded association between blood pressure and CRP elevation in people with hypertension. Individuals with prehypertension or with shorter duration of hypertension (≤1 Year) had significantly a greater likelihood of CRP elevation in comparison to chronic stage-I or stage-II hypertensives.

PLoss of heterozygosity (LOH) of deleted in colorectal cancer (DCC) gene and predisposition to colorectal cancer: Significant association in colorectal cancer patients of Kashmir

1 Department of Biochemistry Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir – 190 011. India. 2 Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir – 190 011. India. 3 Department of Biotechnology, University of Kashmir, Srinagar Kashmir.190011.India. 4 Department of general surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir – 190 011. India.

Serum Leptin Levels, Leptin Receptor Gene (LEPR) Polymorphism, and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18–5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8, CI = 1.6–85.1, p = 0.002] and an inverse association with cardiac disorder [OR = 0.09, CI = 0.02–0.46, p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4, p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.

The XRCC1 Arg399Gln Gene Polymorphism and Risk of Colorectal Cancer: a Study in Kashmir

BACKGROUND The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. MATERIALS AND METHODS A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. RESULTS Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. CONCLUSIONS We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.

Activated H-ras gene mutations in transitional cell carcinoma of urinary bladder in a Kashmiri population

Aims and background The primary aim of the study was to evaluate the incidence of H-ras specific point mutations among a group of Kashmiri patients diagnosed with bladder cancer. We also explored the correlation of clinic-pathological status of the illness with these mutations. Methods and study design The DNA samples of both tumor and normal tissue were evaluated for the occurrence of H-ras activating mutations in exon 1 and 2 by PCR-SCCP and DNA sequencing. In addition, blood was also collected from all the cases to rule out any germ-line mutation. Results Point mutations of activated H-ras identified in bladder cancer patients were 14.5% (7 of 48), including four transversions (two G→T and two A→T) and three transitions (A→G). Of the mutations, 71.4% were detected in codon 61 and 28.6% in codon 12. The pattern of mutation in the study showed a significant association with smoking in bladder tumors (P <0.05). No correlation was found between tumor grade and/or stage and the presence of H-ras mutation. Conclusions Activation of H-ras by mutation plays a less frequent role than other genetic events in the development of the most transitional cell tumors of the bladder in Kashmiri population. Free full text available at www.tumorionline.it

Genetic Variation of ApoE Gene in Ethnic Kashmiri Population and Its Association with Outcome After Traumatic Brain Injury

The outcome from traumatic brain injury (TBI) is variable and only partly explained by known prognostic factors. Genetic factors may influence the brain’s susceptibility to injury or capacity for repair and regeneration. ApoE has been implicated in modifying neurological outcome after TBI, although the mechanisms by which this occurs remain poorly defined. Apolipoprotein E is an apparently multifunctional protein involved in the response of the brain to injury and in subsequent repair processes. Several studies have shown that patients with APOE e4 have a poorer outcome after TBI. This study was aimed to analyse the genotypes of ApoE in Kashmiri population and to examine the association of APOE genotype with outcome after TBI. A total of 450 subjects (300 healthy controls and 150 TBI patients) were recruited for the study. Genotyping was done by PCR-restriction fragment length polymorphism (RFLP).Our study indicated Apoe3/e3 to be the most common genotype in this study group. The allele frequency of the Apo E gene in these study subjects was observed to be 0.07 for the e2 allele, 0.82 for the e3 allele and 0.11 for the e4 allele. However, no association between the presence of APOe4 allele and outcome after head injury was observed in this study [p = 0.92]. Thus, genotype containing the e4 allele (e4/e3 and e4/e4) was not associated with unfavourable outcome after TBI in Kashmiri population.

Role of the Functional Polymorphism of Survivin Gene (-31G/C) and Risk of Breast Cancer in a North Indian Population

&NA; This study was conducted to explore survivin promoter gene ‐31G/C polymorphism and the risk of breast cancer in kashmiri population. For this study 190 pathologically confirmed breast cancer patients, in addition to 200 distinct cancer‐free controls were included. Single nucleotide polymorphism genotyping for ‐31G/C polymorphism in the survivin promoter region was done using a polymerase chain reaction‐restriction fragment length polymorphism method. The combined prevalence of genotype GC+CC was significantly higher in patients (54.1%) compared with the control group (46.5%) (P = .02). The odds ratio (ORs) analysis indicated that the presence of homozygous CC genotype was associated with increased risk for development of breast cancer and the gene frequencies for G and C alleles were statistically different between patient and control groups. Together these results suggest the association of ‐31G/C survivin polymorphism at a genotypic and allelic level in breast cancer. Introduction: Survivin is an apoptosis inhibitor and plays a primary role in cancer development and progression. One of the most common polymorphism of the survivin promoter ‐31G/C (rs9904341) influences its expression and is associated with the risk of cancer development. This study was conducted to explore survivin promoter gene ‐31G/C (rs9904341) polymorphism and the risk of breast cancer. Patients and Methods: The study group included 190 pathologically confirmed breast cancer patients, in addition to 200 distinct cancer‐free controls from Jammu and Kashmir region of India, where breast cancer is the most common cancer in women. Single nucleotide polymorphism genotyping for ‐31G/C polymorphism in the survivin promoter region was done using a polymerase chain reaction‐restriction fragment length polymorphism method. Results: The variant genotype/allele was found in 54.1% of the cases compared with 46.5% of controls. The combined prevalence of genotype GC+CC was significantly higher in patients compared with the control group (P = .02). Analyses of odds ratios (ORs) in the patient and control groups indicated that the presence of homozygous CC genotype was associated with increased risk for development of breast cancer (OR, 2.04; 95% confidence interval [CI], 1.07‐2.98). The gene frequencies for G and C alleles were statistically different between patient and control groups (OR, 1.37; 95% CI, 1.03‐1.84). Conclusion: The results suggest the association of ‐31G/C survivin polymorphism at a genotypic and allelic level in breast cancer.