APOE-E4 allele as a potential marker for implantation failure: A comparison between fertile women, ART success and RIF patients.

OBJECTIVE: Apolipoprotein E (APOE) is the most important precursor for the production of steroid hormones and is also involved in regulating the function of steroid hormones, hence playing a significant role in reproductive processes. So, APOE gene expression may be correlated with the implantation process. This study tries to make a better clarification of the correlation between APOE gene polymorphisms and recurrent implantation failure (RIF), where we compared the frequency of APOE polymorphisms in RIF patients, assisted reproductive treatment (ART) success cases and fertile women. METHOD: In all, 100 women with successful ART who got pregnant (fetal heart rate positive) in their first or second cycle of in vitro fertilization or intracytoplasmic sperm injection, 100 infertile RIF cases, and 100 normal fertile control cases with at least one live birth were included in present study. Following DNA extraction, genotypes were determined through polymerase chain reaction-restriction fragment length polymorphism method using HhaI restriction enzyme. Finally, statistical analysis was performed by chi-squared (χ2) test in SPSS software (P < 0.05). RESULTS: The RIF group showed significantly higher frequency for E3/E4 genotype (29%) compared with the other two control groups (fertile = 15%, ART success [ART+] = 13%) (P = 0.007). There was also a significantly higher frequency of the E4 allele in the RIF group (14.5%) compared with both of the control groups (fertile = 7.5%, ART+ = 6.5%) (P = 0.018). CONCLUSION: APOE4 is correlated with recurrent failure in the process of embryo implantation and, accordingly, it may potentially be considered a possible risk factor to the implantation process. The presence of E4 can be proposed as a predictive indicator in determining the results of assisted reproductive techniques.

APOE polymorphism status (E4) may help in predicting the risk of recurrent implantation failure.

OBJECTIVE: To examine the association between apolipoprotein E (APOE) gene polymorphisms and incidence of recurrent implantation failure (RIF). METHODS: In a case-control study, 100 women with RIF were compared with 100 women with at least one live child. DNA was extracted from the peripheral blood and APOE genotyping was performed through polymerase chain reaction, followed by restriction fragment length polymorphism. Statistical analysis was performed using Pearson's χ2 test. RESULTS: Our data revealed a significantly higher frequency for the E3/E4 genotype and E4 allele in the RIF group compared with controls. Significant differences in frequencies of the E4 allele (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.131-4.185; P = 0.026) and E3/E4 genotype (OR 2.203; 95% CI 1.092-4.443; P = 0.038) were observed between the groups. CONCLUSION: The E4 polymorphism is correlated with RIF occurrence in women undergoing assisted reproductive treatment and potentially can be considered as a risk factor to the human implantation process.

Detection of Human Papillomavirus Genotypes and Major BRCA Mutations in Familial Breast Cancer.

Breast cancer is a multistep disease and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process. High-risk human papillomaviruses (HPVs) are the causative agents of several cancers. In this study, we investigated HPV genotypes associated with breast cancer and its relationship with BRCA mutation for the detection of familial breast cancer. We analyzed 84 formalin-fixed, paraffin-embedded tissue blocks from 38 familial breast cancer and 46 nonfamilial breast cancer samples by multiplex polymerase chain reaction and clinical parameters. Overall prevalence of HPV infection was 27 of 84: 10 (37.03%) HPV-16, 9 (29.62%) HPV-18, 4 (14.81%) HPV-11, 1 (3.7%) HPV-31, 1 (3.7%) HPV-33, and 2 (7.4%) HPV35. Furthermore, 17 mtDNA4977 deletions and 5 5382insC mutations were detected from 38 familial breast cancer samples. Our results demonstrate that infection with HPV was prevalent among Iranian women with familial breast cancer and the testing of mtDNA4977 deletions and 5382insC mutations in combination with clinical parameters as major risk factors can serve in the identification of familial breast cancer.