ABSTRACT
A 66-year-old Japanese man receiving systemic chemotherapy for advanced gastric cancer presented with exertional dyspnea. D-dimer was elevated in the blood. Echocardiography revealed pulmonary hypertension, and a ventilation-perfusion scan indicated decreased perfusion in the bilateral lungs. Cardiac catheterization showed no evidence of pulmonary artery embolization and revealed cytologically confirmed adenocarcinoma. Thus, pulmonary tumor thrombotic microangiopathy (PTTM) was diagnosed. The patient died of respiratory failure on the 17th hospitalization day despite systemic chemotherapy. Retrospective serological testing revealed increased vascular endothelial growth factor in the pulmonary artery blood. This is a rare case with antemortem cytologically proven PTTM mediated by VEGF.
Subject(s)
Lung Neoplasms , Neoplastic Cells, Circulating , Stomach Neoplasms , Thrombotic Microangiopathies , Aged , Humans , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/metabolism , Male , Neoplastic Cells, Circulating/pathology , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/pathology , Retrospective Studies , Stomach Neoplasms/complications , Stomach Neoplasms/diagnosis , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Tomography, X-Ray Computed , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Previous studies suggest that elevated total homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which correlates with plasma total homocysteine levels, are risk factors for schizophrenia (SCZ). Recently, a large genome-wide association study (GWAS) of plasma total homocysteine levels in individuals of European ancestry identified many single-nucleotide polymorphisms (SNPs) (n=13,974). The primary purpose of this study was to examine the association between these plasma total homocysteine-related SNPs and SCZ in the Japanese population. First, we investigated associations between six SNPs and plasma total homocysteine levels in non-psychiatric subjects in the Japanese population (n=1030). Then, we evaluated the cumulative effects of three SNPs on SCZ risk by calculating the Genotype Risk Score (GRS) (1120 cases, 2643 controls). Of the six SNPs examined, we replicated similar associations with the European GWAS at four loci (CENPQ, CPS1, MTHFR, and MUT). GRS based on three SNPs (CENPQ, CPS1, and MTHFR) was significantly associated with SCZ. Our findings suggest that common polygenic variations, which are associated with the plasma total homocysteine levels, may contribute to the risk of SCZ.
