ABSTRACT
Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.
ABSTRACT
BACKGROUND: Depressive disorders are common during pregnancy. There is compelling evidence that the inflammatory response system is important in the pathophysiology of depression. Higher concentrations of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α) in depressed subjects have been described. Because several polymorphisms in the TNF-α promoter region are known to affect its gene expression, the aim of this study was determine whether TNF-α - 857C/T, -308G/A, and -238G/A polymorphisms confer susceptibility to depression during pregnancy in a Mexican mestizo population. METHODS: This case-control study involved 153 depressed pregnant women and 177 controls. Polymorphisms were genotyped using real-time PCR. Odds ratios (OR) and 95% confidence intervals adjusted by age, body mass index, number of pregnancies, months of pregnancy and number of abortions were used to estimate risk. RESULTS: The -857CT genotype was found to increase the risk for depression (OR= 1.73, 95% CI= 1.06-2.82). In contrast, the -238GA genotype reduced the risk (OR= 0.33, 95% CI= 0.14-0.72). The - 308G/A polymorphism was not associated with risk for depression. Finally, the C857-G308-A238 haplotype was associated with a decreased risk of depression (OR= 0.35, 95% CI= 0.15-0.82). CONCLUSION: Our results show for the first time an association between TNF-α -857C/T and -238G/A polymorphisms and prenatal depression in Mexican mestizo population.
