Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

Abstract

The etiology of multiple sclerosis (MS) is still not known, but the interaction of genetic, immunological, and environmental factors seem to be involved. This study aimed to investigate genetic alterations and the vitamin D status in patients with relapsingremitting MS (RRMS) and secondary progressive MS (SPMS). A total of 53 patients (29 RRMS; 24 SPMS) and 25 healthy subjects were recruited to evaluate the micronucleated cell (MNC) frequency and nuclear abnormalities in the buccal mucosa, gene expression profiling in mononuclear cells, and plasmatic vitamin D concentration in the blood. Results showed a higher frequency of cells with karyorrhexis (SPMS) and lower frequencies of nuclear pyknosis (RRMS and SPMS) and karyolysis (SPMS) in patients with MS. Significant increase in the frequency of MNC was detected in the buccal mucosa of RRMS and SPMS patients. HIF1A, IL13, IL18, MYC, and TNF were differentially expressed in MS patients, and APP was overexpressed in cells of RRMS compared to SPMS patients. No relationship was observed between vitamin D level and the differentially expressed genes. In conclusion, the cytogenetic alterations in the buccal mucosa can be important indicators of genetic instability and degenerative processes in patients with MS. Furthermore, our data introduced novel biomarkers associated with the molecular pathogenesis of MS.

MicroRNA-22 Level in Patients with Multiple Sclerosis and Its Relationship with Vitamin D and Vitamin D Receptor Levels

“…However, these results are contradictory to a previous study that showed no significant difference in the VDR expression profile between MS patients and healthy controls [31]. Also, another study that did not coincide with our findings demonstrated that VDR mRNA levels were upregulated in RRMS patients compared to healthy controls.…”

Micronúcleos: Actualización del papel en la inestabilidad genética, inflamación, envejecimiento y cáncer. Revisión panorámica.

“…Se debe destacar que los pacientes con EAi al compararlos con sujetos sanos son más vulnerables a alteraciones genómicas, ya que muestran mayor daño al DNA, intercambio de cromátides hermanas (ICH) y alta frecuencia de células micronúcleadas e inestabilidad genómica en linfocitos y células epiteliales (22,38); como ocurre en pacientes con diabetes mellitus tipo 1 y 2 (22,53), tiroiditis de Hashimoto y Graves (50,53), esclerosis múltiple (54) o Behçet, en cuyos pacientes el daño es mayor durante el periodo activo, donde presentan altas concentraciones de especies reactivas de oxígeno y malondialdehido, disminución de glutatión peroxidasa (GSH-Px) y superóxido dismutasa en plasma (42).…”