The MACROD2 rs6110695 A>G Polymorphism and the Metabolites Indoleacrylic Acid and Butyrylcarnitine Potentially Have Clinical Relevance to WBC Count Prediction

Abstract

Our previous study suggested that the Mono-ADP ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism is significantly associated with white blood cell (WBC) count in the Korean population. The present study aimed to evaluate the clinical relevance of the MACROD2 rs6110695 A>G polymorphism for predicting WBC count by utilizing plasma metabolites and a single-nucleotide polymorphism (SNP). Two groups were characterized by MACROD2 rs6110695 A>G SNP genotypes among 139 healthy subjects based on the genetic information provided in our previous work: rs6110695 AA genotype group (n = 129) and rs6110695 AG genotype group (n = 10). Plasma global metabolic profiling was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). To estimate the predictive abilities of WBC count models using the rs6110695 genotype and/or significant differential metabolites, multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were conducted. The AG genotype had greater WBC-to-apolipoprotein (apo) A-I ratios; counts of WBCs, lymphocytes, monocytes, and granulocytes; monocyte-to-lymphocyte ratio (MLR); and monocyte-to-platelet ratio (MPR) than the AA genotype. In terms of metabolic profile, indoleacetic acid, and butyrylcarnitine levels were considerably distinct between the two groups, and these metabolites were considered to be meaningful prognostic variables for the rs6110695 genotype. Finally, ROC curve analysis demonstrated that the model containing the rs6110695 genotype and the two main metabolites was reliable. The present study revealed that individuals carrying the rs6110695 AG genotype with high plasma indoleacrylic acid and butyrylcarnitine levels might have elevated WBC counts. The rs6110695 genotype and the concentrations of indoleacrylic acid and butyrylcarnitine could contribute to reducing the risk of chronic diseases in the future.