Abstract
OBJECTIVE: Cardiovascular and metabolic diseases, including both obesity and blood pressure, have been previously implicated in observational studies as having some association with the occurrence of adrenal tumors. This study aims to evaluate the causal relationships of these high-risk factors with the disease using a Mendelian randomization approach with two-sample data. Single nucleotide polymorphisms (SNPs) for blood pressure, body mass index (BMI), blood glucose, and cardiovascular diseases were extracted from publicly available whole-genome databases. They were then compared separately with benign adrenal tumors. It was found that only BMI was associated with the occurrence of benign adrenal tumors, and this process may be mediated by C-reactive protein (CRP). We explored whether C-reactive protein (CRP) can mediate the causal relationship between body mass index (BMI) and benign adrenal tumors, further investigating the mechanism and the proportion of CRP involved in this process. METHODS: Utilizing a two-sample Mendelian randomization approach, comparisons were made between BMI, blood pressure, cardiovascular diseases, blood glucose, and the outcome. Subsequently, both two-sample Mendelian randomization and multivariable Mendelian randomization (MVMR) analyses were conducted to investigate whether CRP serves as a mediator in the causal relationship between BMI and benign adrenal tumors, while calculating the proportion of mediation involved. RESULTS: There was no causal relationship observed between blood pressure (OR = 0.976, 95% CI = 0.931-1.024, P = 0.339), blood glucose (OR = 0.960, 95% CI = 0.648-1.422, P = 0.840), cardiovascular diseases (OR = 0.724, 95% CI = 0.244-2.142, P = 0.559), and benign adrenal tumors. However, a positive causal relationship was found between BMI and benign adrenal tumors (OR = 1.20, 95% CI = 1.06-1.35, P = 0.003). There was also a positive causal relationship observed between BMI and CRP (OR = 1.07, 95% CI = 1.06-1.08, P < 0.01), as well as between CRP and benign adrenal tumors (OR = 1.350, 95% CI = 1.058-1.722, P = 0.001). After adjusting for CRP, the causal relationship between BMI and benign adrenal tumors diminished (OR = 1.044, 95% CI = 0.911-1.970, P = 0.067). Even after controlling for BMI, a causal relationship between CRP and benign adrenal tumors persisted (OR = 1.32, 95% CI = 1.035-1.693, P = 0.025). The proportion of mediation by CRP was calculated to be 10.4%. CONCLUSION: Using Mendelian genetic research methods, this study provides evidence that elevated levels of C-reactive protein may serve as a crucial mediating factor in BMI-induced benign adrenal tumors. Therefore, clinicians should pay particular attention to monitoring and managing levels of C-reactive protein when dealing with obese patients, to more effectively prevent the development of adrenal tumors.