RESUMEN
Mitochondrial DNA mutations that lead to mitochondrial dysfunction have long been proposed to play important roles in the development of pancreatic cancer. Of these, alterations to mitochondrial tRNA genes constitute the largest group. Most recently, a variation at position 12307 in the gene encoding tRNA(Leu(CUN)) has been reported to be associated with this disease. However, the molecular mechanism underlying this relationship remains poorly understood. To assess this association, we evaluated this variant by evolutionary conservation analysis, measurements of allelic frequencies among control subjects, and use of several bioinformatic tools to estimate potential structural and functional alterations. We found this residue to have a high conservation index; however, the presence of the A12307G variation in control subjects revealed by a literature search suggested it to be common in human populations. Moreover, RNAfold results showed that this variant did not alter the secondary structure of tRNA(Leu(CUN)). Through the application of a pathogenicity scoring system, this variant was determined to be a "neutral polymorphism," with a score of only 4 points based on current data. Thus, the contribution of the A12307G variant to pancreatic cancer needs to be addressed in further experimental studies.
Asunto(s)
ADN Mitocondrial/genética , Estudios de Asociación Genética , Neoplasias Pancreáticas/genética , ARN de Transferencia de Leucina/genética , Evolución Molecular , Predisposición Genética a la Enfermedad , Humanos , Mutación , Conformación de Ácido Nucleico , Neoplasias Pancreáticas/patología , Polimorfismo de Nucleótido SimpleRESUMEN
In patients with sickle cell anemia, the sickling of red blood cells is known to cause end-organ damage by infarction. In some men who are affected by sickle cell anemia, the obstruction of venous outflow of the penis causes priapism, which could lead to erectile dysfunction. There is also evidence that the disease is linked to other reproductive issues in men-specifically delayed puberty, low testosterone, and sperm abnormalities-although the causes of these problems are less clear. Treatment of sickle cell anemia can have effects on the reproductive system as well. This review summarizes the findings from various publications pertaining to reproductive endocrinology, along with their conclusions and discrepancies.