ABSTRACT
BACKGROUND AND AIMS: The contribution of genetic factors to the susceptibility for developing schizophrenia is well established. Several hypotheses have been developed in an attempt to identify the pathophysiological mechanisms in schizophrenia, with several findings implicating an important role for apoptosis. A limited number of studies investigated the effects of polymorphisms in apoptotic genes on the susceptibility to schizophrenia in different ethnic groups, with none involving an Arab population. The aim of the present study was to investigate the association between multiple polymorphisms in genes for the central apoptotic protein p53 and its regulator NQO1 and the susceptibility for developing schizophrenia in an Arab population from Syria. METHODS: The studied polymorphisms included exon 4 G>C Arg72Pro (rs1042522), IVS3 16 bp Del/Ins (rs17878362), and MspI IVS6+62A>G (rs1625895) of the TP53 gene, and C609T of the NQO1 gene. The study cohort consisted of 90 patients and 144 healthy controls. Association with each of the four polymorphisms was tested under numerous genetic models. The four polymorphisms were genotyped simultaneously using a quadruplex Tetra-Primer ARMS-PCR method described earlier. The combined effects of polymorphisms in NQO1 and TP53 genes were examined. RESULTS: No statistically significant association was found for any of the four polymorphisms. CONCLUSIONS: Our results do not support an association between the studied polymorphisms and schizophrenia in the Syrian population.
Subject(s)
Genes, p53 , Genetic Predisposition to Disease , NAD(P)H Dehydrogenase (Quinone)/genetics , Polymorphism, Genetic , Schizophrenia/genetics , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Syria , Tumor Suppressor Protein p53/geneticsABSTRACT
The folate-homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate-homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06-2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04-6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29-0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97-5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate-homocystiene metabolic pathway genes.
Subject(s)
Ferredoxin-NADP Reductase/genetics , Genetic Association Studies , Genetic Predisposition to Disease/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic/genetics , Schizophrenia/genetics , Adult , Alleles , Cohort Studies , Female , Genotype , Humans , Male , Schizophrenia/enzymology , SyriaABSTRACT
BACKGROUND: The Val158Met single nucleotide polymorphism of the COMT gene has been implicated in the aetiology of schizophrenia, although results from different populations have been conflicting. AIMS: The aim of the present study was to investigate possible association between schizophrenia and Val158Met in a novel Arab population from Syria. METHODS AND MATERIALS: 71 unrelated schizophrenic subjects (45 men) and 102 unrelated healthy controls (62 men) were recruited to take part in this case- control study. The Val158Met of the COMT gene was genotyped for patients and controls, using a new optimized PCR-RFLP method. RESULTS: the results demonstrated that there is no statistically significant difference between the two groups. CONCLUSION: This study does not support that Val158Met has an influence on susceptibility for schizophrenia in this population.
