Promoter methylation and Ile105val polymorphism of GSTP1 gene in the modulation of colorectal cancer risk in ethnic Kashmiri population

BACKGROUND: Glutathione-S-transferases (GSTs) are the most important phase II enzymes of the xenobiotic pathway responsible for the detoxification of carcinogens. GSTP1 gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates thus resulting in increased cancer susceptibility. GSTP1 promoter methylation is also frequently associated with tumor development or poor prognosis in a wide range of tumors. AIM: In this study, we examined the role of genetic polymorphism and promoter methylation of GSTP1 gene in the context of modulation of risk of colorectal cancer (CRC) in Kashmiri population. METHODS: This study used tissue tumor samples (114) and blood samples from (160) patients with CRC and 200 blood samples from healthy donors. GSTP1 polymorphism was studied using polymerase chain reaction (PCR)-restriction fragment length polymorphism and methylation using methylation-specific PCR. RESULTS: There was no significant association between GSTP1 I105V genotypes and the CRC (P>0.05). However, we found a significant association of the Val/Val variant genotype with the dwelling and smoking status (P-value < 0.05). Overall, the homozygous variant Val/Val genotype was associated with a modestly elevated risk for CRC (OR = 1.57; 95% CI = 0.67–3.57). Methyl-specific-PCR analysis revealed 25.4% methylation of the GSTP1 promoter in CRC cases and was not found to be statistically significantly associated with clinicopathological parameters of the CRC cases (P>0.05). Also, no significant associations of any of the three genotypes with promoter hypermethylation were observed. CONCLUSION: We conclude that promoter hypermethylation in homozygous GSTP1 mutants did not elevate the risk of CRC in Kashmiri population.

Role of TLR4 gene polymorphisms in the colorectal cancer risk modulation in ethnic Kashmiri population - a case-control study

Background: Colorectal carcinogenesis has been found to be associated with the polymorphic status of Toll-like receptor 4 gene in various populations of the world

Aim: The aim of the study was to determine the genetic association of TLR4 gene polymorphisms [Asp299Gly and Thr399Ile] with disease susceptibility and risk development in colorectal cancer [CRC] patients of Kashmir, India

Materials and methods: Genotype frequencies of TLR4 polymorphisms [Asp299Gly and Thr399Ile] were compared between 120 CRC patients and 200 healthy controls using PCRRFLP method

Results: We did not find any significant association between the TLR4 gene polymorphisms and the CRC cases [p>0.05]. However CT genotype [Thr399Ile] showed modest elevated risk of the development of CRC [OR = 1.78 95% CI [0.88-3.5]]. Also G allele [AG genotype] of TLR-4 Asp299Gly polymorphism was found to be significantly associated with the male gender [p value = 0.006] and involvement of Nodes [p value = 0.01] whereas, T allele [CT genotype] of Thr399Ile polymorphism showed significant association with the smoking status [p value = 0.03]

Conclusion: Our results suggest that TLR4 gene polymorphism is not a key modulator of the risk of developing colorectal cancer in Kashmiri population

Gross and fine motors functional impairments in children with cerebral palsy: a cross-sectional study

Objective: To assess prevalence of gross and fine motor functional impairments in children with CP

Methods: This cross sectional study was conducted at Department of Developmental and Behavioural Paediatrics, The Children's Hospital and Institute of Child Health, Lahore from October, 2014 to September, 2015. Atotal of 100 CP patients were taken to assess for gross and fine motor functional impairment, using Gross Motor Functional Classification System [GMFCS] and Bimanual Fine Motor Function [BFMF] scales. All data were analyzed using SPSS version 20

Results: In this hospital-based study comprised 100 children with a diagnosis of CP with 2 to 8 years of age were ascertained. The mean age of patients was found as 4.090 +/- 1.672 years. Study group included 32 females and 68 males. GMFCS was found at level I in 5% patients, level II in 18% patients, level III in 16% patients, level IV in 15% patients and level V in 46% patients. The corresponding percentages for BFMF were 21.7% patients, 18% patients, 15% patients, 13% patients and 33% respectively. Among oral musculature problems, drooling was the most common problem [68 %]. Larger proportion of gross motor functional impairment were associated with the spastic type of cerebral palsy [p=0.03], more specifically quadriplegic cerebral palsy [p=0.000]. Also a larger number of patients with fine motor functional impairments were associated with spastic type of cerebral palsy [p=0.009], more precisely quadriplegic cerebral palsy [p=0.000]

Conclusion: It is concluded that quadriplegic spastic CP was the most frequent type that had the worst motor impairment hence making patients functionally dependant in activities of daily livings

Exenatide's effect in reducing weight and glycosylated hemoglobin level in an Arab population with type 2 diabetes

To determine whether exenatide is effective in reducing weight and glycosylated hemoglobin level [HbA1c], and to investigate its efficacy in improving lipid profile, blood pressure, and creatinine levels in the Arab population. This study was conducted at the Endocrine Unit, Dubai Hospital, Dubai, United Arab Emirates. We retrospectively collected data from patients with type 2 diabetes started on exenatide between November 2011 and February 2012. Data included demographics, clinical, laboratory results, and medications used. A general linear model adjusted by baseline characteristics [weight, HbA1C, age, use of statins, and duration of diabetes] was used to assess changes between baseline and end of trial in HbA1C, weight, low density lipoprotein cholesterol, total cholesterol, triglycerides, creatinine, and blood pressure. After 6 months of treatment with exenatide, the HbA1c decreased by 0.47% [95% confidence level [CI]: -0.01 - 0.95] [p=0.055]. Weight reduction was highly significant; 5.6 kg [95% CI: 3.34 - 7.85] [p<0.001]. Those reductions remained significant after adjustment for confounding factors. This study showed that weight reduction was highly significant with exenatide. The borderline significance in HbA1c reduction can be attributed to the small sample size