High prevalence of Y chromosome partial microdeletions in overweight men

Microdeletions of the Y chromosome are one of the most frequent genetic causes of spermatogenic failure in infertile men. But their role in gaining weight is unclear. The present study investigated the possible association of these partial microdeletions and obesity. In a case-control study, 180 males were selected. The prevalence of microdeletions was assessed using PCR in AZFc area of Y chromosome and statistical analysis was done using the Fisher exact test and Pearson correlation. In our study, inverse relationship was observed between body mass index and testosterone level [p-value: 0.005]. Fisher exact tests showed that there was a significant association between gr/gr mutation and BMI [p-value: 0.044]. Our study revealed that Y chromosome microdeletions are more common in obese men. Furthermore, microdeletions such as gr/gr, which were observed in normal men, could cause decreased testosterone level. So, they may contribute to gaining weight

RNAi induced inhibition of MRP1 expression and reversal of drug resistance in human promyelocytic HL60 cell line

Multidrug resistance [MDR] is a complex phenomenon in which many different genes regulating drug transport, cellular repair, detoxification and drug metabolism are involved. Nevertheless, in most drug resistant cell lines and cancer patients up-regulation of ABC-transporter genes such as MDR associated Protein [MRP1] gene could be at the basis of the drug resistance phenotype. We aimed to decrease MRP1 expression at the mRNA level to modulate drug resistance phenotype in the methotrexate-resistant HL60 cell line. We designed a small interfering RNA [siRNA] molecule against MRP1 and applied it to HL60 cell line in a 0 to 72 hours time range. siRNA could specifically inhibit gene expression by 80% of the initial mRNA level with in 36 to 48 hours. The siRNA-treated cells demonstrated 100-fold reduction in methotrexate [MTX] resistance compared to untreated cells. The data indicate that this approach may be applicable to the study of MRP1 expression and development of future strategies to reverse the MRP1 dependent drug-resistance phenotype in tumors back to a drug-sensitive one