Single nucleotide polymorphism E23K of KCNJ11 gene and other risk factors associated with type-2 diabetes mellitus in Gaza

Type 2 diabetes mellitus (T2DM) is a multifactorial disease in which environmental triggers interact with genetic variants in predisposition to disease. The aim of this study was to evaluate (E23K) SNP in KCNJ11 gene as a possible contributor to T2DM among Gaza City patients. Also to consider relation between E23K SNP and other risk factors for T2DM. Two hundred male and female individuals were examined: 100 T2DM patients and 100 control individuals. The glucose level was determined, and the groups were genotyped for the SNP (E23K) by PCR/RFLP technique using the BanII restriction enzyme. A questionnaire was completed to evaluate the role of physical and environmental risk factors for T2DM. There was a strong statistically significant relation between the E23K polymorphism and T2DM (P= 0.000). Forty three percent of cases were E/K compared to 29% of controls; and 15% of cases were K/K compared to 3% of controls. Obesity, persistent stress, absence of physical activity and low level of education were also significantly related to T2DM (P= 0.000). The mean fasting blood sugar level was significantly higher among the cases than the control, and particularly among homozygous and heterozygous cases (P= 0.000). In conclusion, risk factors that are significantly related with T2DM patients in Gaza city include the E23K polymorphism, obesity, persistent stress, absence of physical activity, and low level of education. The inheritance of the K allele predisposes for T2DM, provided that other genetic or/and physical and environmental risk factors be present

Thiopurine methyltransferase genotyping in Palestinian childhood acute lymphoblastic leukemia patients

The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of the present study was to determine the frequency of TPMT polymorphisms and their association with the occurrence of adverse events, during 6-mercaptopurine therapy in pediatric acute lymphoblastic leukemic (ALL) patients in Gaza Strip. A total of 56 DNA samples from all pediatric ALL patients admitted to the pediatric hematology departments of Gaza strip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated and the TPMT*2, TPMT*3B TPMT*3A and TPMT*3C allelic polymorphism was determined by PCR-RFLP and allele specific PCR technique. No TPMT*2, *3B or *3C alleles were detected. Only one, out of 56 patients, was found heterozygous for the TPMT*3A allele. Thus, the frequency of TPMT*3A allele was calculated to be 0.89%. Fourteen patients of ALL were suffering from myelotoxicity during 6-MP therapy. From our results, no significant association could be established between clinical and laboratory data and/or the presence of the mutation in TPMT gene. TPMT*3A was the only deficiency allele detected in our population with an allelic frequency of 0.89%. Other polymorphic alleles in TPMT gene, or factors other than TPMT polymorphisms may be responsible for the development of myelosuppression in cases that don’t carry the investigated TPMT alleles (*2, *3A, *3B and *3C

CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in Palestinian population

Abstract Objective The genetic polymorphism (rs16969968 in CHRNA5, and rs1051730 in CHRNA3 genes) were recently shown to be associated with risk of LC. The aim of this study is to elucidate whether they predispose Palestinian individuals to lung cancer, and how is this related to smoking. Results Frequency of the rs16969968-A allele was significantly higher in the case group (36.7%) than in normal controls (17.5%; P = 0.022; OR = 6.83 for AA and 2.81 for AG genotypes). The frequency of rs1051730-T allele was also significantly higher in the case group (46.7%) than in the control group (22.5%; P = 0.001; OR = 2.20 for TC and 13.22 for TT genotypes). Frequency of rs16969968-A allele was higher in smokers (29.1%) than nonsmokers (15.7%) regardless of lung cancer; similarly, frequency of rs1051730-T allele was also higher in smokers than in smokers (46.7% vs 22.5%, respectively). The higher the proportion of the risk allele (rs16969968-A and rs1051730-T), the higher the mean number of daily consumed cigarettes (P = 0.006). Carrying rs16969968-A and/or rs1051730-T alleles results in an increased risk to lung cancer probably by increasing the individual’s tendency for heavy smoking. The allelic frequency of the rs16969968-A and rs1051730-T alleles among normal Palestinian controls is similar to different populations worldwide