Study of the Association of CYP2D6*4 Polymorphism with the Susceptibility of HCV-Related Liver Cirrhosis and Liver Cancer

Abstract: Background: CYP2D6 is a member of cytochrome P450 enzymes family which is involved in detoxification of a wide range of xenobiotics and drugs. Several genetic polymorphisms had been shown to affect its activity which may results in increased susceptibility to malignant disorders. Aim: to detect if there is specific cytochrome CYP2D6*4 genotype associated with hepatocellular carcinoma or hepatic cirrhosis among patients with hepatitis C. Method: CYP2D6*4 genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). This study includes 23 patients with hepatic cirrhosis, 26 patients with HCC and normal 19 subjects with matched age and sex. Results: The frequency of (Extensive metabolizers) EM genotype (wild type) was higher in HCC cases compared to cirrhotic patients and controls (76.8% versus 39.1% and 63.2%).The frequency of (intermediate metabolizers) IM genotype (heterozygous variant) was higher in cirrhotic cases compared to HCC patients and controls (52.2% versus 15.4% and 26.3 %). On contrary, the frequency of (poor metabolizers) PM genotypes (homozygous variant) was the lowest among HCC patients in comparison to cirrhotic patients and controls (3.8% vs 8.7% and 10.5% respectively). Higher frequency of IM and PM genotypes were observed in patients more than 45 years old in cirrhotic and malignant patients. Frequency of IM and PM were significantly higher in males than females in HCC patients (p=0.000). Frequency of p allele was higher in males than females and in older patients than younger patients in the three groups. Conclusions: These data indicate that PM CYP2D6*4 genotype has no role in development of HCC and IM genotype may have a role in developing hepatic cirrhosis, while higher frequency of EM genotype may contribute to the progression of HCC in HCV-infected subject

Influence of prolactin and estrogen on disease activity in patients with systemic lupus erythematosus

Objective The objective of this paper is to evaluate the role of prolactin and estrogen levels on disease activity in patients with systemic lupus erythematosus (SLE). Patients and methods This study included 60 female patients with SLE, with a mean age of 33.5±13.12 years. It was conducted between November 2014 and October 2015. Disease activity was defined according to Systemic Lupus Erythematosus Activity Index; score of at least 6 was considered as an active disease. Prolactin (PRL) and estrogen levels and other serological markers of lupus disease activity, namely, complement 3,4 (C3 and C4), erythrocyte sedimentation rate, C-reactive protein, and anti-double-stranded DNA (anti-dsDNA) titer were calculated. Results Hyperprolactinemia was present in 25.0% of patients, and low estrogen level was present in 33.3% of patients. There was no significant correlation between either of estrogen or prolactin levels and all clinical and laboratory features, except for a significant positive correlation between anti-dsDNA and hyperprolactinemia. Conclusion There was no significant correlation between either of PRL or estrogen levels and Systemic Lupus Erythematosus Activity Index score. Overall, 80.0% of patients with hyperprolactinemia and 80.0% with low estrogen level had SLE activity. There was a significant difference in the frequency of further indicators of disease activity in SLE such as raised erythrocyte sedimentation rate, raised C-reactive protein, or decrease in complement factors with high serum PRL and low estrogen level