Systematic screening of the LDL-PLA2 gene for polymorphic variants and case-control analysis in schizophrenia
Systematic screening of the LDL-PLA2 gene for polymorphic variants and case-control analysis in schizophrenia
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DOI：
10.1006/bbrc.1997.7741
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发表时间：
1997-12-29
影响因子：
3.1
通讯作者：
Gloger, IS
中科院分区：
文献类型：
--
作者：
Bell, R;Collier, DA;Gloger, IS
使用微卫星标记对基因组进行系统扫描已确定染色体 6p21.1 是多受影响家庭中精神分裂症的假定基因座。一系列研究也有证据表明磷脂代谢异常在精神分裂症中的作用。根据这些发现以及血小板激活因子在神经传递和神经发育中的作用，我们检查了 LDL-PLA(2)（血浆 PAF 乙酰水解酶，PAF-AH）基因，这是一种丝氨酸依赖性磷脂酶，已通过杂交作图定位到染色体 6p21.1，作为精神分裂症的位置候选基因。使用 SSCP/HD 分析系统地筛选了该基因的与疾病相关的多态性。该基因内发现了四种多态性变异，并在 200 名精神分裂症患者和 100 名对照者中进行了研究。发现外显子 7 中的变异 (Iso195Thr) 与精神分裂症有弱相关性 (p = 0.04)，而外显子 11 中的变异 (Val379Ala) 几乎达到显着性 (p = 0.057)。经过多次测试校正后，没有检测到显着的关联。结合多态性对的单倍型分析也没有提供该基因与我们的患者样本中的精神分裂症相关的证据。 (C) 1997 年学术出版社。
Systematic scans of the genome using microsatellite markers have identified chromosome 6p21.1 as a putative locus for schizophrenia in multiply affected families. There is also evidence hom a series of studies for a role of abnormal phospholipid metabolism in schizophrenia. In light of these findings, and the role of platelet activating factor in neurotransmission and neurodevelopment, we have examined the LDL-PLA(2) (plasma PAF acetylhydrolase, PAF-AH) gene, a serine dependent phospholipase that has been mapped by hybrid mapping to chromosome 6p21.1, as a positional candidate gene for schizophrenia. The gene was systematically screened using SSCP/HD analysis for polymorphisms associated with the disease. Four polymorphic variants were found within the gene and studied in a group of 200 schizophrenic patients and 100 controls. The variant in exon 7 (Iso195Thr) was found to be weakly associated with schizophrenia (p = 0.04) and the variant in exon 11 (Val379Ala) almost reached significance (p = 0.057). After correcting for multiple testing no significant associations mere detected. Haplotype analysis combining pairs of polymorphisms also provided no evidence for association of this gene with schizophrenia in our sample of patients. (C) 1997 Academic Press.