Proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia susceptibility: a meta-analysis

Abstract

Previous studies have been conducted to explore the association between proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia (SZ) susceptibility, but providing the controversial results. Here we performed this meta-analysis to determine whether PRODH variants were associated with SZ risk. Relevant studies were screened by retrieving online database PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and SZGene from inception to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on genotype data or allele frequency to evaluate the strength of this association. For rs372055, eleven studies with 3398 SZ patients and 3171 controls were included and the results indicated that people carrying the T allele was not associated with SZ risk in allele frequency model (C vs T, OR = 1.12, 95%CI = 0.96-1.32). However, results from subgroup analysis showed a significant relationship between rs372055 and SZ risk in dominant genetic model (CC + CT vs TT, OR = 1.26, 95% CI = 1.05-1.50) and heterogeneous model (CT vs TT, OR = 1.26, 95% CI = 1.05-1.52) in Asian, but not in Caucasian. For polymorphisms rs383964, rs450046, rs385440 and rs2870983, no associations were found between these polymorphisms and SZ susceptibility in allele frequency. This meta-analysis suggests that rs372055 (C/T) polymorphism in PRODH gene is associated with increased SZ risk only in Asian.

Coexisting Conditions Modifying Phenotypes of Patients with 22q11.2 Deletion Syndrome

“…Although the latest research does not support the theory that high proline level is responsible for psychosis, it cannot be excluded that nullisomy of the PRODH gene has no clinical effect. Despite the association between variants in PRODH and an increased risk of schizophrenia shown in some studies, the potential role of this gene in psychiatric diseases remains unclear [ 36 , 37 ].…”

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…CCR4 [407], CCR2 [408], CD48 [409], CD28 [410], CCL3 [411], CTLA4 [412], C6 [413], MICB (MHC class I polypeptide-related sequence B) [414], DRD3 [415], HGF (hepatocyte growth factor) [416], DIO3 [417], TTR (transthyretin) [418], GRHL3 [419], VEGFA (vascular endothelial growth factor A) [420], ADM (adrenomedullin) [421], CHI3L1 [422], SOX3 [423], MAG (myelin associated glycoprotein) [424], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [425], SREBF1 [426], OLIG2 [427], ATF3 [428], NGFR (nerve growth factor receptor) [429], TF (transferrin) [430], GLUL (glutamate-ammonia ligase) [324]. MOG (myelin oligodendrocyte glycoprotein) [431], ERBB3 [432], NHLH2 [433], GADD45B [434], PADI2 [435], ADORA1 [436], NINJ2 [437], WNT7A [438], DAO (D-amino acid oxidase) [439], PRODH (proline dehydrogenase 1) [440] and HCRTR1 [441] could regulate the development of psychiatric disorders. CCR2 [442], FASLG (Fas ligand) [443], GPNMB (glycoprotein nmb) [444], NPY2R [445], TRPM8 [446], TTR (transthyretin) [447], ADM (adrenomedullin) [448], CHI3L1 [375], CDH1 [377], HIP1R [449], SEMA4D [450], HAPLN2 [451], MYRF (myelin regulatory factor) [452], BIN1 [453], BMP2 [454], APLP1 [391], SEPTIN4 [455], DAO (D-amino acid oxidase) [456], TKTL1 [347], ADAP1 [457], HPDL (4-hydroxyphenylpyruvate dioxygenase like) [458], NME3 [459], SPON1 [460] and LGALS3BP [225] were revealed to be altered expressed in neurodegenerative diseases.…”

Proline Metabolism in Neurological and Psychiatric Disorders

“…Prolonged disturbances in cell metabolism are likely to lead to neuronal dysfunction, which in turn triggers a series of neurological and psychiatric diseases. PRODH polymorphisms are significantly associated with schizophrenia susceptibility ( Guo et al, 2018 ). There is also evidence that defects in PRODH lead to glutamatergic and GABAergic neuron dysfunctions ( Crabtree et al, 2016 ).…”

“…Conversely, glutamate is converted into a P5C intermediate through P5C synthase (P5CS) and further reduced to proline by P5C reductases (PYCRs). All of the enzymes in the proline metabolism pathway have been reported to be associated with neurological or psychiatric disorders in human and animal models ( Table 1 ) ( Guo et al, 2018 ; Li et al, 2021 ; Liu et al, 2009 ).…”