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Association between Schizophrenia and Lipoprotein Lipase Gene

Author: XieCui
Tutor: YangMaoSheng
School: Chongqing Medical University
Course: Genetics
Keywords: Lipoprotein lipase (LPL) gene Common complex disease Schizophrenia (SZ) Association study Genetic variants
CLC: R749.3
Type: Master's thesis
Year: 2011
Downloads: 36
Quote: 0
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Abstract


The lipoprotein lipase （LPL） gene encodes a rate-limiting enzyme protein that has a key role in the hydrolysis of triglycerides. Hypertriglyceridemia, one widely prevalent syndrome of LPL deficiency and dysfunction, may be a risk factor in the development of dyslipidemia, typeПdiabetes （T2D）, essential hypertension （EH）, coronary heart disease （CHD） and Alzheimer’s disease （AD）. Findings from earlier studies indicate that LPL may have a role in the pathology of these diseases and therefore is a common or shared biological basis for these common complex diseases. To examine this hypothesis, we reviewed articles on the molecular structure, expression and function of the LPL gene, and its potential role in the etiology of diseases. Evidence from these studies indicate that LPL dysfunction is involved in dyslipidemia, T2D, EH, CHD, and AD; and support the hypothesis that there is a common or shared biological basis for these common complex disease.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 where the LPL gene is located. Therefore, LPL is an attractive candidate gene for schizophrenia and we tested this hypothesis in a case-control sample.We collected the blood sample of 319 schizophrenia patients and 575 ethnic-, age-, sex-matched controls. Genomic DNAs were extracted from peripheral venous blood leukocytes, adjusted to 10ng/ul and stored at -20 oC for genotyping. Nine tag single nucleotide polymorphisms （SNPs） with minor allele frequency （MAF） >5%, were selected from the HapMap database. All the SNPs in our study were genotyped with Taqman genotyping assays. Individual SNP was tested for association with the phenotype using a 2x2 contingency table to calculate aχ2 statistic.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=3.21×10-8) and genotypes (OR 3.08, 95%CI 2.07-4.56; global p=7.88×10-9), respectively. Interestingly, this association only replicated in the male (p=5.87×10-9 for allele; p=1.79×10-11 for genotype) but not in the female samples （p>0.05）. After correcting for multiple testing, the above association remains significance (pc<1×10-6). These results suggest that rs253 C allele and CC genotype confer risk for schizophrenia in the males.These results suggest that rs253 in LPL might be a risk polymorphism of schizophrenia and lend support to the potential role of lipid metabolism in schizophrenia and further investigations are warranted.

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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Schizophrenia
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