Risk factors for K-RAS proto-oncogene mutation in colorectal cancer

K-rats is an important onco-gene on chromosome 12 and encodes p21 Ras-protein, which is a growth promoting protein. Specific point mutations in codons 12 and 13 are prevalent in colorectal cancer [CRC] patients. Recognition of K-ras mutations may be helpful in screening and early diagnosis of CRC. This study aimed at investigating the association between potential variables known or suspected to be related to risk of CRC and occurrence of K-ras mutations, explaining how such variables play a role in CRC tumorigenesis. Eighty CRC patients were examined for RBC folic acid by enzyme chemi-luminescence and K-ras proto-oncogene genotyping for codon 12 mutations by enriched PCR-RELP technique. RBC folic acid level was significantly deficient in CRC patients with K-ras mutation [23 patients, mean RBC folate= 100.96+51.3 ng/ml] than those without the mutation [57 patients, mean RBC folate = 216.6+116.4 ng/ml][P<0.01], suggesting that decreased folic acid may be a risk factor for K-ras mutation development. Gender also was found to be another predicting risk factor, in spite of being masked by the accentuated folic acid deficiency in females. Folic acid supplementation should be mandatory, and those at high-risk of CRC should be screened for the risk of K-ras mutation using the prediction equation method depending on sex and RBC folate followed by close monitoring for those a high risk for the mutation

Genetic polymorphisms of plasminogen activator inhibitor-1, vascular endothelial growth factor and angiotensin converting enzyme among pre-eclamptic women

Pre-eclampsia is one of the leading causes of maternal as well perinatal morbidity and mortality. The exact pathogenesis of pre-eclampsia is most likely multifactorial. Polymorphisms of plasminogen-activator inhibitor-1 [PAI-1], vascular endothelial growth factor [VEGF] and angiotensin converting enzyme [ACE] may contribute to the pathogenesis of pre-eclampsia. This study was conducted to evaluate the PAI-1, VEGF and ACE genetic polymorphisms in pregnant women with and without pre-eclampsia. A total of 42 pre-eclamptic women and 20 women with normotensive pregnancy, aged between 20-43 years were enrolled in this study. Genomic DNA was isolated from peripheral blood leucocytes. The 4G/5G polymorphism of the PAI-1 gene and insertion-deletion polymorphism of the ACE gene were detected in DNA samples with the use of the polymerase chain reaction [PCR] and the 936 C/T polymorphism of the VEGF gene was determined by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. Chi-squared and student t-tests were used for statistical analysis. In pre-eclampsia [n=42 women], the frequencies of 4G4G and 4G5G genotypes of PAI-1 gene were significantly higher [14.3% and 57.1% respectively] than in the normotensive pregnant controls [0% and 15%, respectively], P<0.001. The 4G allele frequency was significantly higher in pre-eclampsia [42.9%] than pregnant controls [7.5%]; P<0.001. Besides, no difference was detected in the ACE [I/D] and VEGF [936C/T] genotypes distribution of pre-eclampsia and normal pregnancy. The 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene is suggested to be a genetic risk factor for pre-eclampsia

Genetic polymorphism of uridine-diphosphoglucuronosyl transferase 1A7 gene in chronic viral hepatitis and hepatocellular carcinoma

Hepatocellular Carcinoma [HCC] is the most common cause of primary liver neoplasm and the fourth most frequent type of cancer worldwide causing one million deaths per year. Genetic polymorphisms of UDP-glucuronosyltransferases [UGTs], which detoxifies endogenous and environmental carcinogen, have been reported to be associated with HCC. The present study aimed to elucidate the role of UGT1A7 SNP [622 T-C] in the pathogenesis of Hepatocellular Carcinoma [HCC] and whether this polymorphism is associated with elevated bilirubin level or not. This study was conducted on 22 patients with HCC, 25 patients with chronic viral hepatitis B and/ or C and 16 apparently healthy controls. All subjects underwent laboratory tests for Liver and Kidney functions, serological markers [HBV and HCV] and serum AFP as a tumor marker, Genomic DNA from the blood was analyzed for UGT1A7 polymorphism using PCR-RFLP. The prevalence of HCV infection was higher in HCC group compared to other groups. AFP-level significantly increased in HCC than in viral hepatitis and control [p<0.0005]. A statistically significant increase was found in the frequency of risky genotypes [TC, CC] in HCC group as compared to the protective genotype [TT] [P<0.01]. UGT1A7 T allele and C allele were designated as H [high activity] and L [low activity] alleles, respectively. A statistically significant increase was found in frequency of L allele in HCC group [54%] as compared to control group [25%] p=0.03. On the other hand, the H allele showed statistically significant decrease in HCC group [46%] compared to control group [75%] p=0.03. Increase in total bilirubin level in cases harboring UGT 1A7 Polymorphism compared to wild genotype [p<0.01] was observed demonstrating its role in the pathogenesis of hyperbilirubineamia. The UGT1A7 polymorphism was associated with elevated bilirubin level and may play a role in the pathogenesis of HCC

Paraoxonase gene polymorphism and serum paraoxonase activity: relationship with type I diabetes and nephropathy

Human serum paraoxonase-I [PON1] is physically associated with high density lippprotein [HDL] and has been implicated in the prevention of LDL lipid peroxidation. PON1 gene displays several polymorphisms that influence both its level of expression and its catalytic activity. The goal of this study was to examine the association between paraoxonase-1 [PON1] activity and gene polymorphism and the micro-vascular complications in children and adolescence suffering from type 1 DM [TIDM]. Case-control study. One study centre at a University hospital. Thirty eight patients, with type 1 diabetes [n=38], 13 patients presenting with diabetic nephropathy [mean age 18.76 +/- 5.59 years. 8 males and 5 females] and 25 without diabetic nephropathy [mean age 14.48 +/- 3.69 years. 14 males and 11 females] and 16 healthy controls [mean age 12.38 +/- 8.25 years, 10 males and 6 females]. The allele variants of PON1 gene polymorphisms in the PON1 coding region Q192R and L55M have been identified by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Serum PON1 enzyme activity was measured spectrophotometrically. Serum PON1 activity was significantly decreased in complicated diabetics when compared to both non-complicated patients and the control persons [103.33 +/- 35.46 nmol/ml/min, 462.57 +/- 200.69 nmol/ml/min and 1132 +/- 317.61 nmol/ml/min respectively]. As regards PON1 Q192R polymorphism, the R allele was more frequent in complicated diabetics versus both non-complicated diabetics and controls [p=0.0113 and p=0.001 respectively]. PON1 192QR genotype is a risk factor for developing type 1 diabetes OR=7.8; 95% CI [1.12-65.7] with p=0.043. PON1 192QR genotype and 192R allele are risk factors for developing micro-vascular complications with OR =6.40 and 4.00; 95% CI [1.44.28.29] and [1.15-13.87] with p=0.01 and 0.023 respectively. In PON1 L55M polymorphism, non significant differences in the genotype or allele frequency were found between T TIDM, both complicated and non-complicated diabetics and control persons. The association of PON1 Q192R polymorphisms, lower PON1 activity and poorer diabetic control found in patients with diabetic nephropathy further support an idea of genetic factors contributing to development of vascular complications in diabetes