五羟色胺转运体及神经肽S受体基因多态性与原发性失眠的致病机制研究  

Study on the pathogenic mechanism of serotonin transporter gene and neuropeptide S receptor gene polymorphism and primary insomnia

作　　者：范杰 谢宇平[1,2] 惠培林 马薇[1,2] 王金凤 苏晓艳[1,2] 陈雪萍 王旭斌[1,2] 郭斌 赵媛[1,2] FAN Jie;XIE Yuping;HUI Peilin;MA Wei;WANG Jinfeng;SU Xiaoyan;CHEN Xueping;WANG Xubin;GUO Bin;ZHAO Yuan(Sleep Medicine Center,Gansu Provincial People’s Hospital,Lanzhou 730000,China;Gansu Sleep Clinical Medical Research Center,Lanzhou 730000,China)

机构地区：[1]甘肃省人民医院睡眠医学中心,甘肃兰州730000 [2]甘肃省睡眠临床医学研究中心,甘肃兰州730000

出　　处：《中国实用神经疾病杂志》2022年第11期1321-1330,共10页Chinese Journal of Practical Nervous Diseases

摘　　要：目的研究五羟色胺转运体(5-HTT)基因和神经肽S受体(NPSR)基因的多态性、连锁不平衡及单倍型与原发性失眠(PI)发生的相关性。方法利用生物信息学方法和国际HapMap计划以及NCBI公布的人群中的单核苷酸多态性(SNP)数据,构建出单体型域,并结合功能提示,共挑选5个5-HTT及13个NPSR等位基因频率>5%的单体型标签SNP位点。共收集157例原发性失眠症患者和133例年龄、性别相匹配的正常对照组,抽取静脉血分离后对5个5-HTT及13个NPSR标签SNP位点进行测序,利用SHEsis在线软件对所选SNP位点基因型及等位基因进行连锁不平衡和单倍型分析,得出结果。结果所有SNP位点基因型在对照组中符合Hardy-Weinberg平衡检测(P>0.05)。失眠组与对照组的年龄、性别差异无统计学意义(均P>0.05)。NPSR的SNP位点rs323920的T/C型与健康对照组比较差异有统计学意义(P=0.042),NPSR的SNP位点rs324957的A/G型与健康对照组比较差异有统计学意义(P=0.023)。连锁不平衡分析结果显示,5-HTT-SNP位点rs140700与rs6352之间存在完全连锁不平衡,13个NPSR SNP位点两两间进行连锁不平衡分析,发现多个位点之间存在完全连锁不平衡。单倍型结果分析示,5-HTT-SNP位点CGTT单倍型在PI组和对照组中的差异有统计学意义(P<0.05)。NPSR-SNP位点CACGGTCCCCAGC单倍型在PI组和对照组中的差异有统计意义(P<0.01)。结论神经肽S基因多态性rs323920位点和rs324957位点可能是原发性失眠的易感基因位点,NPSR的SNP单体型rs323920的基因型T>C变异和rs324957基因型的A>G变异可能是原发性失眠的易感基因,5-HTT和NPSR SNP位点的连锁不平衡与原发性失眠相关,NPSR-SNP位点CACGGTCCCCAGC单倍型组合为原发性失眠人群的危险基因,原发性失眠发生率显著升高。5-HTT和NPSR基因在原发性失眠的遗传病因中可能起着一定作用。Objective To investigate the correlation between polymorphisms,linkage imbalance and haplotypes of serotonin transporter(5-HTT)gene and neuropeptide S receptor(NPSR)gene and primary insomnia(PI).Methods A single nucleotide polymorphism(SNP)data in the population was constructed using bioinformatics methods and international Hap Map projects and NCBI to construct a haplotypic domain,and a total of 55-HTT and 13 NPSR allele frequency>were selected in combination with functional prompts 5%of haplotype tag SNP sites.A total of 157 patients with primary insomnia and 133 normal control groups matched by age and sex were collected,venous blood was collected and sequenced 55-HTT and 13 NPSR-tagged SNP sites,and the linked imbalance and haplotype analysis of the selected SNP locus genotype and allele were analyzed by SHEsis online software.Results All SNP locus genotypes in the control group were in line with the Hardy-Weinberg equilibrium assay(P>0.05).There were no significant differences in age and sex between insomnia group and control group(all P>0.05).The difference between the T/C type of the SNP locus rs323920 and the healthy control group was statistically significant(P=0.042),and the difference between the A/G type of the SNP locus rs324957of NPSR and the healthy control group was statistically significant(P=0.023).The linkage imbalance analysis results showed that there was a complete linkage imbalance between the 5-HTT-SNP sites rs140700 and rs6352,and the linkage imbalance analysis was carried out between the 13 NPSR SNP sites,and it was found that there was a complete linkage imbalance between multiple sites.The analysis of haplotype results showed that the difference between the 5-HTT-SNP site CGTT haplotype in the PI group and the control group was statistically significant(P<0.05).The difference of NPSR-SNP locus CACGGTCAGC haplotypes in the PI group and the control group was statistically significant(P<0.01).Conclusion The rs323920 and rs324957 polymorphisms of neuropeptide S gene may be susceptibility l

关 键 词：五羟色胺转运体基因 NPSR基因 原发性失眠 单核苷酸多态性 连锁不平衡 单倍型 

分 类 号：R747.9[医药卫生—神经病学与精神病学]