# Association between peripheral blood serum phenylalanine to tyrosine ratio and the risk of moyamoya disease: a case-control study

## TL;DR

This study found that higher levels of phenylalanine to tyrosine ratio in blood are linked to increased risk of moyamoya disease, suggesting it could be a useful biomarker.

## Contribution

The study identifies a novel association between serum phenylalanine/tyrosine ratio and moyamoya disease risk in adults.

## Key findings

- Serum phenylalanine/tyrosine ratio was significantly higher in moyamoya disease patients compared to healthy controls.
- Elevated phenylalanine/tyrosine ratio was positively associated with increased risk of moyamoya disease after adjusting for traditional risk factors.
- Adding phenylalanine/tyrosine ratio to conventional risk factors improved moyamoya disease risk prediction.

## Abstract

Phenylalanine (Phe) and its metabolite tyrosine (Tyr) have been shown to play an important role in the mechanisms and development of cardiovascular and cerebrovascular disease, and its ratio (Phe/Tyr) has been suggested to be an important indicator of inflammation. It was uncertain whether Phe/Tyr is associated with higher risk of MMD. Therefore, we conducted this study to evaluate the relationship between Phe/Tyr and the risk of MMD and its subtypes.

A total of 360 adult MMD patients and 89 age-matched healthy controls (HCs) were consecutively recruited for this prospective study. We measured peripheral blood serum Phe and Tyr levels in all participants to analyze the association between Phe/Tyr and the risk of MMD and its subtypes.

Serum Phe/Tyr was significantly higher in MMD patients and their subtypes than in HCs (p < 0.01). After adjusting for traditional risk factors, Phe/Tyr was positively associated with the risk of MMD (OR: 14.035, 95%CI: 2.784–70.748, p = 0.001). When Phe/Tyr was assessed in quartile subgroups, the third quartile (Q3) and fourth quartile (Q4) subgroups of Phe/Tyr had a significantly increased risk of MMD compared to the first quartile (Q3, OR: 2.019, 95%CI: 1.066–3.824, p = 0.031; Q4, OR: 2.887, 95%CI: 1.446–5.765, p = 0.003). The risk of MMD subtypes also increased with elevated Phe/Tyr level. Meanwhile, the addition of Phe/Tyr to conventional risk factors could significantly improve the risk prediction for MMD.

In this study, the risk of MMD increased with elevated Phe/Tyr, suggesting that peripheral blood serum Phe/Tyr may be a valuable predictive biomarker of adult MMD.