上海地区脑梗死患者肝脂酶基因启动子4个位点的连锁不平衡分析

目的：探讨上海地区脑梗死患者肝脂酶启动子250G／A、514C／T、710T／C和763A／G基因的单核苷酸多态性（SNP）位点及其构成的单倍型和连锁不平衡关系。方法：运用聚合酶链反应-限制性片段长度多态性技术,对脑梗死组（133例）和健康对照组（112名）进行肝脂酶基因多态性分析。结果：与健康对照组相比,脑梗死组的-250G／A、-514C／T基因型和等位基因频率分布差异均有统计学意义（均P〈0．05）;与健康对照组相比,脑梗死组的-710T／C、-763A／G基因型和等位基因频率分布差异无统计学意义（均P〉0．05）。同时配对连锁不平衡检验表明,-250G／A与-514C／T、-710T／C、-763A／G之间,-514C／T与-710T／C、-763A／G之间,以及-710T／C与-763A／G之间均存在强连锁不平衡。另外,等位基因-250G与-514C、-710C、-763G以及-514C与-710C、-763G分别配对时,在脑梗死组的出现率明显低于在对照组的出现率;等位基因-250A与-514T、-710T、-710C、-763G,-514T与-710C、-763G以及-710T与-763G分别配对时,在脑梗死组的出现率明显高于在对照组的出现率。结论：上海地区脑梗死患者肝脂酶基因4个SNP位点之间存在着有意义的单倍型和连锁不平衡关系,并且单倍型GC、GG以及CC可能降低脑梗死的发病率。而单倍型AT、AC、AG、TC以及TG可能提高脑梗死的发病率。

The linkage disequilibrium of four loci in hepatic lipase promoter gene of cerebral infarction patients in Shanghai

OBJECTIVE: To investigate the single nucleotide polymorphism (SNP), the distribution of their haplotypes and linkage disequilibrium of hepatic lipase (HL) gene promoter 250G/A, 514C/T, 710T/C and 763A/G in cerebral infarction patients of Shanghai. METHODS: Peripheral blood sample were collected from 133 patients with cerebral infarction and 112 healthy controls in Shanghai. The HL gene polymorphism was analyzed by polymerase chain reaction- restriction fragment length polymorphism. RESULTS: There were statistically significant differences in genotype and allele frequencies between the healthy controls and the patients with cerebral infarction in -250G/A and -514C/T genotypes and allele frequencies (all P < 0.05). However, there were no significant differences in genotype and allele frequencies in -710T/C and -763A/G between the healthy controls and the patients with cerebral infarction (all P > 0.05). Besides, there was a strong linkage disequilibrium between -250G/A and -514C/T, -710T/C, and -763A/G respectively, between -514C/T and -710T/C and -763A/G respectively, and between -710T/C and -763A/G. When the haplotypes were -250G/-514C, -250G/-710C, -250G/-763G, -514C/-710C, and 514C/-763G respectively, the frequencies in the cerebral infarction group were significantly lower than that in the healthy controls. When the haplotype was -250A/-514T, -250A/-710T, -250A/-710C, -250A/-763G, -514T/-710C, -514T/-763G, and -710T/-763G respectively, the frequencies in the cerebral infarction group were significantly higher than those in the healthy controls. CONCLUSION: There are significant haplotypes and linkage disequilibrium among the four SNPs of HL gene in the cerebral infarction patients of Shanghai. The haplotypes GC, GG, and CC lower the incidence rate of cerebral infarction, while the haplotypes AT, AC, AG, TC, and TG increase the incidence rate of cerebral infarction.