RESUMO
BACKGROUND: The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. METHODS: This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. RESULTS: The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. CONCLUSION: HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.
Assuntos
Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Neoplasias Ovarianas , Pró-Proteína Convertase 9 , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Hidroximetilglutaril-CoA Redutases/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Pró-Proteína Convertase 9/genética , Hipolipemiantes/uso terapêutico , Hipolipemiantes/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Introduction: Type 2 diabetes (T2DM) stands as a global chronic illness, exerting a profound impact on health due to its complications and generating a significant economic burden. Recently, observational studies have pointed toward a potential link between Chronic Obstructive Pulmonary Disease (COPD) and T2DM. To elucidate this causal connection, we employed the Mendelian randomization analysis. Method: Our study involved a two-sample Mendelian randomization (MR) analysis on COPD and T2DM. Additionally, tests for heterogeneity and horizontal pleiotropy were performed. Results: For the MR analysis, 26 independent single nucleotides polymorphisms (SNPs) with strong associations to COPD were chosen as instrumental variables. Our findings suggest a pronounced causal relationship between COPD and T2DM. Specifically, COPD emerges as a risk factor for T2DM, with an odds ratio (OR) of 1.06 and a 95% confidence interval ranging from 1.01 to 1.11 (P = 0.006). Notably, all results were devoid of any heterogeneity or pleiotropy. Conclusion: The MR analysis underscores a significant causal relationship between COPD and T2DM, highlighting COPD as a prominent risk factor for T2DM.
