Clinica chimica acta; international journal of clinical chemistry · 2025
A large-scale multicenter study of reference intervals and clinical potential for homocysteine-folate cycle metabolites in Northern Chinese population.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Guo Tongyao, Wan Lingling, Liu Li, Song Xiaoxu, Wang Ziwei, Yin Yue, Li Yining, Yue Zhihong, Pei Lin, Wang Hui, Jia Mei, Shi Hongjun, Cao Lin-Lin
Аннотация
OBJECTIVES: The study was conducted to establish the reference intervals of homocysteine-folate cycle metabolites based on the healthy population from multiple centers in northern China, and determine their clinical significance in the diagnosis of related diseases.
METHODS: 1222 healthy individuals were recruited from four hospitals in northern China. The levels of serum HCY-related metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to determine whether the reference intervals needed to be split by age, gender and region. The development and evaluation of machine learning (ML) models were conducted to determine the clinical value of these metabolites.
RESULTS: A robust LC-MS/MS method was established to measure ten homocysteine-folate cycle metabolites simultaneously. The reference intervals of these HCY-related metabolites were determined using large-scale and multicenter data. The age-, gender- and region-dependent variation were evaluated, and gender differences were found in HCY, MET and 5-MTHF, age differences were observed in BET, VB6 and MMA, while MET was found to be different in various cities. Multiple ML models were established based on homocysteine-folate cycle metabolites, and the results showed that not only HCY, but also other metabolites showed diagnostic potential for cardiovascular disease (CVD), cerebrovascular disease (CBVD), chronic kidney disease (CKD) and merely hypertension patients. These ML models will be useful for screening of high-risk population and early diagnosis of HCY-associated diseases.
CONCLUSIONS: Our study established the age-, gender- and region-specific reference intervals of homocysteine-folate cycle metabolites, and determined their clinical significance in CVD, CBVD, CKD and merely hypertension.
METHODS: 1222 healthy individuals were recruited from four hospitals in northern China. The levels of serum HCY-related metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to determine whether the reference intervals needed to be split by age, gender and region. The development and evaluation of machine learning (ML) models were conducted to determine the clinical value of these metabolites.
RESULTS: A robust LC-MS/MS method was established to measure ten homocysteine-folate cycle metabolites simultaneously. The reference intervals of these HCY-related metabolites were determined using large-scale and multicenter data. The age-, gender- and region-dependent variation were evaluated, and gender differences were found in HCY, MET and 5-MTHF, age differences were observed in BET, VB6 and MMA, while MET was found to be different in various cities. Multiple ML models were established based on homocysteine-folate cycle metabolites, and the results showed that not only HCY, but also other metabolites showed diagnostic potential for cardiovascular disease (CVD), cerebrovascular disease (CBVD), chronic kidney disease (CKD) and merely hypertension patients. These ML models will be useful for screening of high-risk population and early diagnosis of HCY-associated diseases.
CONCLUSIONS: Our study established the age-, gender- and region-specific reference intervals of homocysteine-folate cycle metabolites, and determined their clinical significance in CVD, CBVD, CKD and merely hypertension.