The association of tryptophan and phenylalanine are associated with arsenic-induced skin lesions in a Chinese population chronically exposed to arsenic via drinking water: a case-control study.

OBJECTIVES: We investigated the association of specific serum amino acids (AAs) with the odds of arsenic-induced skin lesions (AISL) and their ability to distinguish patients with AISL from people chronically exposed to arsenic. DESIGN: Case-control study. SETTING: Three arsenic-exposed villages in Wuyuan County, Hetao Plain, Inner Mongolia, China were evaluated. PARTICIPANTS: Among the 450 residents aged 18-79 years, who were chronically exposed to arsenic via drinking water, 56 were diagnosed as having AISL (defined as cases). Another 56 participants without AISL, matched by gender and age (±1 year) from the same population, were examined as controls. MAIN OUTCOME MEASURES AND METHODS: AA levels were determined by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics analysis. Potential confounding variables were identified via a standardised questionnaire and clinical examination. Multivariable conditional logistic regression model and receiver operating characteristic curve analyses were performed to investigate the relationship between specific AAs and AISL. RESULTS: Tryptophan and phenylalanine levels were negatively associated with AISL (p<0.05). Compared with that in the first quartile, the adjusted OR of AISL in the second, third and fourth quartiles were decreased by 44%, 88% and 79% for tryptophan and 30%, 80% and 80% for phenylalanine, respectively. The combination of these two higher-level AAs showed the lowest OR for AISL (OR=0.08; 95% CI 0.02 to 0.25; p<0.001). Furthermore, both AAs showed a moderate ability to distinguish patients with AISL from the control, with the area under the curve (AUC; 95% CI) as 0.67 (0.57 to 0.77) for tryptophan and 0.70 (0.60 to 0.80) for phenylalanine (p<0.05). The combined pattern with AUC (95% CI) was 0.72 (0.62 to 0.81), showing a sensitivity of 76.79% and specificity of 58.93% (p<0.001). CONCLUSIONS: Specific AAs may be linked to AISL and play important roles in early AISL identification. TRIAL REGISTRATION NUMBER: NCT02235948.