Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, the...Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, there is extreme variability in occurrence and clinical presentation of sickle cell disease which may be explained by some other genetic changes associated with the gene. In the present study we examined the association between HBB gene polymorphism rs33949930 T>C in the occurrence of sickle cell disease in Saudi Arabia population. Materials and Methods: A case control study of 100 sickle cell disease patients and 100 healthy controls from Tabuk, Saudi Arabia. HBB gene rs33949930 T>C polymorphism was analyzed using Allele specific polymerase chain reaction technique. Results: It was observed that the genotype percentages TT, TC and CC among the patients with sickle cell disease were 63.0%, 35.0% and 2.0% and healthy controls were 68.0%, 27.0% and 5.0% respectively. Allele frequency for T allele was observed to be fT = 0.20 and fT = 0.19, where as for C allele was fC = 0.80 and fC = 0.81 among cases and controls respectively (p = 0.29). Compared to the TT genotype, the odds ratio of 1.4 (95% CI 0.76 - 2.57), risk ratio of 1.2 (95% CI 0.86 - 1.65) and risk difference of 8.4 (-6.66 - 23.38) for heterozygous genotype of HBB rs33949930 T>C was observed in relation to sickle cell disease. In addition, some difference in the laboratory values was observed among sickle cell disease patients with the different variants of HBB gene rs33949930 T>C polymorphism, especially the carriers of heterozygous TC genotype;however, the difference doesn’t reach to statically significant number. Conclusion: Present study suggested that there was not any significant association between HBB gene rs33949930 T>C polymorphism and occurrence of sickle cell disease. However, the heterozygous TC genotype of the polymorphism showed some higher ratios among cases as compared to healthy control group.展开更多
Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region o...Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region of BAX results in differential binding capacity of TP53 protein there by regulating its expression, which has been found to be associated with different clinical outcomes in various malignancies. Presently we aimed to analyze the possible impact of the BAX G(-248)A polymorphism on the risk and other clinical features of non-small cell lung cancer in Indian population. The BAX promoter polymorphism was analyzed in blood samples of 320 subjects with 1:1 case/control ratio by primer-introduced restriction analysis PCR and survival curves were plotted using Kaplan-Meier analysis. It was observed that more than 3-fold increased risk of developing non-small cell lung cancer was associated with homozygous AA genotype of BAX G(-248)A promoter polymorphism in Indian population, with more predominant in smokers with pack-year > 45 (heavy) and using cigarette or huka as their smoking source than homozygous GG genotype. Significant associations was observed between TNM stage (p = 0.037) and histological type (0.02), of non-small cell lung cancer patients with the polymorphism. Patients homozygous for A allele exhibited a significant poor overall survival compared with patients displaying GA + AA or GA or GG genotype [median survival 6.0 vs 9.0, 11.0, and 30.0 months, respectively (p < 0.0001)]. Adenocarcinoma and advanced stage patients with AA genotype showed lower median survival time than squamous cell carcinoma and early stage non-small cell lung cancer patients (median 3.0 and 5.0 vs 8.0 and 9.0 months, respectively). We conclude that the genetic polymorphism G(-248)A in the TP53 binding promoter region of pro-apoptotic genes BAX may contribute to the risk of developing non-small cell lung cancer in Indian population and also may be an important factor for adverse clinical outcome for patients with non-small cell lung cancer.展开更多
Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, ...Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.展开更多
文摘Background: Sickle cell disease and sickle cell trait are common erythrocyte disorders that are most often caused by a point mutation (rs334, designated HbS) in the hemoglobin beta gene (HBB);however of this fact, there is extreme variability in occurrence and clinical presentation of sickle cell disease which may be explained by some other genetic changes associated with the gene. In the present study we examined the association between HBB gene polymorphism rs33949930 T>C in the occurrence of sickle cell disease in Saudi Arabia population. Materials and Methods: A case control study of 100 sickle cell disease patients and 100 healthy controls from Tabuk, Saudi Arabia. HBB gene rs33949930 T>C polymorphism was analyzed using Allele specific polymerase chain reaction technique. Results: It was observed that the genotype percentages TT, TC and CC among the patients with sickle cell disease were 63.0%, 35.0% and 2.0% and healthy controls were 68.0%, 27.0% and 5.0% respectively. Allele frequency for T allele was observed to be fT = 0.20 and fT = 0.19, where as for C allele was fC = 0.80 and fC = 0.81 among cases and controls respectively (p = 0.29). Compared to the TT genotype, the odds ratio of 1.4 (95% CI 0.76 - 2.57), risk ratio of 1.2 (95% CI 0.86 - 1.65) and risk difference of 8.4 (-6.66 - 23.38) for heterozygous genotype of HBB rs33949930 T>C was observed in relation to sickle cell disease. In addition, some difference in the laboratory values was observed among sickle cell disease patients with the different variants of HBB gene rs33949930 T>C polymorphism, especially the carriers of heterozygous TC genotype;however, the difference doesn’t reach to statically significant number. Conclusion: Present study suggested that there was not any significant association between HBB gene rs33949930 T>C polymorphism and occurrence of sickle cell disease. However, the heterozygous TC genotype of the polymorphism showed some higher ratios among cases as compared to healthy control group.
文摘Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region of BAX results in differential binding capacity of TP53 protein there by regulating its expression, which has been found to be associated with different clinical outcomes in various malignancies. Presently we aimed to analyze the possible impact of the BAX G(-248)A polymorphism on the risk and other clinical features of non-small cell lung cancer in Indian population. The BAX promoter polymorphism was analyzed in blood samples of 320 subjects with 1:1 case/control ratio by primer-introduced restriction analysis PCR and survival curves were plotted using Kaplan-Meier analysis. It was observed that more than 3-fold increased risk of developing non-small cell lung cancer was associated with homozygous AA genotype of BAX G(-248)A promoter polymorphism in Indian population, with more predominant in smokers with pack-year > 45 (heavy) and using cigarette or huka as their smoking source than homozygous GG genotype. Significant associations was observed between TNM stage (p = 0.037) and histological type (0.02), of non-small cell lung cancer patients with the polymorphism. Patients homozygous for A allele exhibited a significant poor overall survival compared with patients displaying GA + AA or GA or GG genotype [median survival 6.0 vs 9.0, 11.0, and 30.0 months, respectively (p < 0.0001)]. Adenocarcinoma and advanced stage patients with AA genotype showed lower median survival time than squamous cell carcinoma and early stage non-small cell lung cancer patients (median 3.0 and 5.0 vs 8.0 and 9.0 months, respectively). We conclude that the genetic polymorphism G(-248)A in the TP53 binding promoter region of pro-apoptotic genes BAX may contribute to the risk of developing non-small cell lung cancer in Indian population and also may be an important factor for adverse clinical outcome for patients with non-small cell lung cancer.
文摘Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.
