Xie_2011_Psychiatr.Genet_21_307

OBJECTIVE: Many studies have suggested that certain types of lipids such as phospholipids, fatty acids, and cholesterols are involved in the pathology of nervous system diseases. Lipoprotein lipase (LPL), as the key enzyme of triglyceride hydrolysis, is expressed in the brain regions functionally relevant to learning, memory, and other cognitive functions. In addition, both genome-wide linkage and association studies in schizophrenia have implicated the chromosome 8p22 region, in which the LPL gene is located. Therefore, LPL is an attractive candidate gene for schizophrenia and we tested this hypothesis in a case-control sample. METHODS: In this study, we investigated allele and genotype frequencies distributions of nine single nucleotide polymorphisms (SNPs) within the LPL gene in Han Chinese patients with schizophrenia (n=319) and healthy controls (n=575). RESULTS: Significant differences were detected between case and control groups in the frequencies of rs253 alleles [odds ratio (OR): 1.74; 95% confidence interval (CI): 1.43-2.11; P=3.21x10] and genotypes (OR: 3.08; 95%CI: 2.07-4.56; global P=7.88x10), respectively. Interestingly, this association was observed only in the male (P=5.87x10 for allele; P=1.79x10 for genotype) and not in the female samples (P>0.05). After correcting for multiple testing, the above association remains to be significant (Pc<1x10). These results suggest that rs253 C allele and CC genotype confer risk for schizophrenia in men. CONCLUSION: Our study lends support to the potential role of lipid metabolism in schizophrenia and further investigations are warranted.