Brief reportNo association of the rs4646396 SNP in the PEMT locus with schizophrenia in a Chinese case–control sample
Introduction
The phospholipid hypothesis of schizophrenia links schizophrenia to a loss of highly polyunsaturated fatty acids (PUFAs) from membrane phospholipids (Horrobin, 1996, Sumiyoshi et al., 2008). Long-chain PUFAs, such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid, are very important in neural functions as they are stored in the form of phospholipids on the cellular membranes (Kidd, 2007). The phospholipid hypothesis has been supported by findings of biochemical abnormalities of phospholipid metabolism in schizophrenia, including decreased levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and membrane PUFAs in red blood cells, alteration of phosphomonoesters and phosphodiesters in the brain (Komoroski et al., 2008), and increased activity of phospholipase A2 (PLA2) in blood (Law et al., 2006). Genetic analysis also suggests that the gene coding for cytosolic PLA2 may be associated with risk of schizophrenia (Law et al., 2006). Increased breakdown may be one of the major reasons for abnormal metabolisms of membrane phospholipids in schizophrenia, but the involvement of abnormal phospholipid synthesis should also be taken into account. Phosphatidylethanolamine methyltransferase (PEMT) is an important enzyme for PC synthesis by catalysing methylation of PE. In a recent study, we found a strong association of the PEMT gene with schizophrenia in the Chinese family trios consisting of fathers, mothers and affected patients with schizophrenia (Liu et al., 2007). If this association were confirmed, the phospholipid hypothesis would gain further support through genetic analysis. However, replication of initial findings is particularly important to rule out false positive results. The present study was therefore undertaken to apply a case–control design to validate the PEMT finding.
Section snippets
Methods
We recruited a total of 628 patients with schizophrenia and 588 healthy controls for the genetic analysis at the Research Center for Neuroscience & MH Radiobiology Research Unit, Changchun, China. Of 628 patients aged 35.3 ± 12.2 years, 327 (52.1%) were male and 301 (47.9%) were female. Of 588 healthy controls aged 35.4 ± 12.1 years, 365 (62.1%) were male and 233 (37.9%) were female. These participants were all Chinese of Han origin and came from the Northeast area of China. Patients were admitted
Results
SNP rs4646396 is a C to T base change. The χ2 goodness-of-fit test showed that the genotypic distributions of rs4646396 were in Hardy–Weinberg equilibrium in both the patient group (χ2 = 1.44, df = 1, P = 0.23) and the control group (χ2 = 0.94, df = 1, P = 0.33). As shown in Table 1, rs4646396 was not associated with schizophrenia in either male subjects or female subjects.
Discussion
In our previous study, we found that the C allele was preferentially transmitted by parents to their offspring affected with schizophrenia. However, the present work did not show such an association, although the frequency of the C allele was slightly higher in the patient group than in the control group (χ2 = 3.18, df = 1, P = 0.08). The odds ratio (OR) was 1.17 with a 95% confidence interval (CI) of 0.98–1.40 (Table 1).
This case–control study failed to detect a genetic association between the PEMT
Acknowledgements
We thank the patients and healthy volunteers for their support and participation. This work was supported by the National 863 program of China (2004AA221070), the Project — sponsored by SRF for ROCS, SEM, China, and the grant from the National Natural Science Foundation of China (30700257).
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