Association between total protein, albumin, globulin, albumin- globulin ratio and rheumatoid arthritis: evidence from NHANES and Mendelian randomization

Abstract

Background With the increasing incidence of rheumatoid arthritis (RA) and the increasing percentage of serum RF negativity, there is an urgent need for more and more accurate methods for the early diagnosis and prevention of RA, among which serum proteins are closely related to the development of RA and are expected to become new auxiliary diagnostic tools, but their relationship with RA is not clear, so this study aimed to investigate the causal relationship between total protein (TP), albumin (ALB), globulin ( GLB), and albumin-globulin ratio (A/G) on the causal relationship of rheumatoid arthritis (RA). Methods In this study, the relationship between TP, ALB, GLB, A/G and rheumatoid arthritis was comprehensively evaluated by generalized linear modeling and smoothed curve fitting through the data of serum proteins and RA in the NHANES(National Health and Nutrition Examination Survey) database; moreover, for the positive results with significant associations, the inverse variance weighted (IVW) method in Mendelian Randomization (MR) was used in conjunction with the other four methods to further validate and clarify the causative relationship, and finally, the results were subjected to the inspection of heterogeneity and horizontal polytomousness in order to assess whether the results were robust. Results In the observational study, after correction for confounders, TP, GLB, and A/G were not significantly associated with rheumatoid arthritis, whereas ALB was significantly negatively associated with rheumatoid arthritis (OR = 0.662, [95%CI = 0.507–0.864], P = 0.003), and subgroup analyses showed significant negative associations in both males and females (male : OR = 0.674, [95%CI = 0.458–0.991], P = 0.047; females: OR = 0.661, [95%CI = 0.437–0.999], P = 0.049). In further MR analysis, IVW: ALB on RA, OR = 0.70 [95%0.52–0.93], P = 0.013; RA on ALB, OR = 0.95 [95%CI = 0.93–0.98], P < 0.001.The results of the MR analyses remained consistent with NHANES. Conclusion There is a significant relationship between ALB and RA, and the reduction of ALB may be one of the risk factors for RA, as well as one of the outcomes in the development of RA.