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Studies of individual with both SNPs (C677T and A1298C) showed that subjects with heterozygosity for both mutations resulted in an even lower MTHFR activity than heterozygosity for single MTHFR mutations, while no subjects carry both homozygote for MTHFR mutations regardless which SNPs 15 Furthermore, There were studies of multiple polymorphisms of one-carbon metabolism and schizophrenia symptoms showed an increase negative symptoms severity with increase of risk alleles, suggesting a cumulative effects of risk SNPs in one-carbon metabolism 61

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TRPMs are also stimulated by a variety of endogenous agents: TRPM2 activation occurs by ADPR and its analogs, in addition to reactive oxygen species (ROS) (Jimenez et al., 2020

MAPK, mitogen-activated protein kinase

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