Estrogen Receptor Alpha (ESR1) Gene Polymorphisms in Pre-eclamptic Saudi Patients.

OBJECTIVES: Pre-eclampsia causes maternal mortality worldwide. Estrogen receptor alpha (ESR1) gene polymorphisms were responsible for cardiovascular diseases. This case control study was conducted to investigate whether 2 polymorphic genes of ESR1 are associated with pre-eclampsia among Saudi women in Madina city, Saudi Arabia. METHODS: Blood samples from 97 pre-eclamptic and 94 healthy pregnant women were analyzed using restriction fragment length polymorphism-polymerase chain reaction method. All the subjects were recruited randomly from outpatient clinics of Madina Maternity Children Hospital (MMCH), Madina, Saudi Arabia, between Dec. 2012 and Jan. 2014. RESULTS: There was no association between pre-eclampsia and PvuII and XbaI ESR1 gene polymorphisms individually. TT/AA and TT/AG genotype combination existed significantly in pre-eclamptic patients compared to control. The frequency of PvuII and XbaI combined TT/AA genotypes between pre-eclamptic women was 36.1% vs 9.6%, however, frequency of PvuII and XbaI combined TT/AG genotypes between pre-eclamptic women was 3.1% vs 17%, compared to control. The homozygous T-A haplotype carriers showed high pre-eclampsia risk, independent of pregnancy, BMI and smoking status (adjusted odds ratio (OR): 3.26, 95% confidence interval (CI):1.71-9.21). The heterozygous T-A haplotype carriers did not differ from that of non-carriers (adjusted OR: 1.12, 95% CI: 0.47-2.75). No association was observed between pre-eclampsia and T-G, C-G and C-A haplotype of PvuII and XbaIESR1 gene polymorphisms. CONCLUSIONS: T-A haplotype of homozygous associated with pre eclampsia not heterozygous carriers of ESR 1 PvuII and XbaI gene polymorphisms elicited high risk of pre-eclampsia. GG genotype of XbaI polymorphism decreased pre-eclampsia risk. Further studies using larger sample size are recommended to investigate the ESR 1 gene polymorphisms associated with pre-eclampsia.

ssociation of Cytochrome P450-1B1 Gene Polymorphisms with Risk of Breast Cancer: an Egyptian Study.

It is thought that population characteristics of breast cancer may be due to a variation in the frequency of different alleles of genes such as CYP1B1. We aimed to determine the association of CYP1B1 polymorphisms in 200 breast cancer cases and 40 controls by PCR-RFLP. Frequencies were assessed with clinical and risk factors in Egyptian patients. The genotype LV and the Leu allele frequencies for patients and controls were 42.9% and 50%, and 52.9% and 53.3%, respectively), with no significant differences observed (P values = 0.8 and 0.6, respectively). There was also no significant association between genotypes and any risk factors for cases (>0.05) except laterality and metastasis of the tumor (P values=0.006 and 0.06, respectively). The CYP1B1 polymorphism Val432Leu was not associated with breast cancer in Egypt, but may provide clues for future studies into early detection of the disease.

The Role of Genetic Polymorphisms in Nrf2 and P73 in Egyptian Women with Breast Cancer

Background: Breast cancer is the commonest cancer in Egyptian females. Nrf2 is involved in oxidative stress while P73 functions in response to DNA damage. This study aimed to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 SNPs in breast cancer in Egypt. Patients: Eighty-five female patients with breast tumours (41 malignant, 44 benign) were included. Nrf2 (rs6721961) and p73 (G4A) SNPs were determined by PCR- CTPP assay. Results: Genotype frequencies of the Nrf2 promoter SNP were 34.2% and 37.9% for AA in benign and malignant groups respectively, and 43.9% and 40.5% for CC and, 21.9 % and 21.6% for CA. Genotype frequencies for the P73 G4A SNP were 52.9% and 44.7% for GA in benign and malignant groups respectively, and 47.1% and 55.3% for GG. Discussion: Nrf2 genotypes in pre - and post-menopausal patients, showed significantly different distributions in the 2 patient groups, the AA genotype being significantly more common in pre-menopausal patients. The P73 G4A SNP showed no relation to age of disease onset. Conclusion: The Nrf2 (rs6721961) AA genotype might be related to early breast cancer onset. In contrast the P73 G4A polymorphism showed no relation to either disease risk or age at presentation.

Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia.

Cytochrome P450 3A4 (CYP3A4) is the most plentiful cytochrome P450 in adult human liver and small intestine and is responsible for detoxification of more than 50% of drugs in addition to the metabolic deactivation and metabolism of many carcinogens. Polymorphism of CYP3A4-A-290G considered the only allele that appears to stimulate CYP3A4 expression and has been associated with a number of clinical phenotypes, including prostate cancer, breast cancer, leukemia and the early onset of puberty. In this study, we analyzed the presence of CYP3A4-A-290G polymorphism in 77 newly diagnosed AML cases and 72 healthy control using PCR/RFLP aiming to show CYP3A4-A-290G polymorphism pattern in acute myeloid leukemia patients, and its role in disease severity and progression. A highly statistically significant difference was found between the control and AML groups as regards the heterozygous genotype (p-value = 0.002) and increases the risk of AML 11.4-fold. Also there was a highly significant difference between the control and AML patients regarding variant allele (G in AG and GG genotypes) (p-value 0.001) and increases the risk of AML 19-fold. No statistically significant association found between the CYP3A4-A-290G polymorphism and different clinical or laboratory parameters as well as an initial response to treatment, overall survival and the disease free survival. We concluded that CYP3A4-A-290G polymorphism is a genotypic factor that increases the CYP3A4 enzymatic activity and increases the risk of AML by 18.9-fold.

Influence of lipoic acid on testicular toxicity induced by bi-n-butyl phthalate in rats.

Bi-n-butyl phthalate (BNBP) is an environmental pollutant. The aim of this study was to evaluate the protective effect of lipoic acid (LA) against testicular dysfunction associated with the intake of to BNBP- intoxicated rats. Adult male Wistar rats were divided into 4 groups of 6 animals each, and received medication orally for 14 days. Group I rats received 0.5 ml corn oil. Group II rats received LA (20 mg/kg B.W./day). Group III rats received BNBP (250 mg/kg B.W./day). Group IV rats received LA 24h prior to BNBP intake. Testes weight, cauda sperm count and sperm motility were decreased significantly by 18.15%, 13.83% and 13.5%, respectively, after BNBP treatment. Significant increase by 12.1%, 10.20% and 11.51%, respectively, was observed in LA-BNBP rats. Significant increase by 1.53%, 1.5% and 1.8%, for serum follicle stimulating hormone, testosterone and total antioxidant status, respectively, were observed in LA-BNBP rats. Testicular lipid peroxides and lactate dehydrogenase enzyme were significantly decreased by 1.5 and 1.6 folds, respectively, in LA-BNBP rats were decreased after BNBP treatment. Testicular superoxide dismutase, catalase and glutathione reductase enzymes were significantly increased in LA-BNBP rats. LA-BNBP rats, decreased the damage to seminiferous tubules produced by BNBP intake. In conclusion, LA mitigated BNBP-induced testicular toxicity through antioxidant mechanism and by direct free radical scavenging activity.