新疆地区维吾尔族与汉族阿尔茨海默病患者19号染色体代表性基因位点多态性及民族差异研究

Polymorphisms in Alzheimer's Disease-associated Genes on Chr19 in Uygur and Han People with Alzheimer's Disease in Xinjiang:a Comparative Study

背景全基因组关联分析发现,19号染色体上存在数个阿尔茨海默病(AD)相关易感基因,而分析不同民族AD患者相关易感基因多态性对深入研究AD发病机制及治疗措施具有重要意义。目的分析新疆地区维吾尔族与汉族AD患者19号染色体代表性基因位点多态性及民族差异。方法选取2016年8月—2018年6月在新疆医科大学第二附属医院临床神经诊疗中心及乌鲁木齐市六道湾医院、昌吉市人民医院诊治的AD患者131例作为病例组,另选取同期新疆医科大学第二附属医院的体检健康者128例作为对照组。采用聚合酶链式反应(PCR)扩增测序技术分析ABCA7、TOMM40、CD33、GALP基因位点rs3764650、rs2075650、rs3826656、rs3865444、rs3745833基因型及等位基因。分别比较对照组与病例组中维吾尔族、汉族受试者及维吾尔族与汉族AD患者19号染色体代表性基因位点基因型及等位基因频率。结果对照组与病例组rs3764650、rs2075650、rs3826656、rs3865444、rs3745833的基因型及等位基因频率分布符合Hardy-Weinberg遗传平衡定律(P>0.05)。对照组与病例组中汉族受试者rs3764650、rs2075650、rs3826656、rs3865444基因型、等位基因频率及rs3745833基因型频率比较,差异无统计学意义(P>0.05);但rs3745833等位基因频率比较,差异有统计学意义(P<0.05)。对照组与病例组中维吾尔族受试者rs3764650、rs2075650、rs3826656、rs3865444、rs3745833基因型、等位基因频率比较,差异无统计学意义(P>0.05)。维吾尔族与汉族AD患者rs2075650、rs3865444、rs3745833基因型、等位基因频率及rs3826656基因型频率比较,差异无统计学意义(P>0.05);但rs3764650基因型、等位基因频率及rs3826656等位基因频率比较,差异有统计学意义(P<0.05)。CD33基因rs3826656、rs3865444在汉族受试者、维吾尔族受试者及AD患者中均形成连锁不平衡,其中对照组与病例组中汉族、维吾尔族受试者rs3826656-rs3865444单体型GC、AA、AC基因型频率比较,差异均无统计学意义(P>0.05);汉族与维吾尔族AD患者rs3826656-rs3865444单体型GC、AA基因型频率比较,差异无统计学意义(P>0.05);但维吾尔族AD患者rs3826656-rs3865444单体型AC基因型频率高于汉族AD患者(P<0.05)。结论GALP基因位点rs3745833多态性可能与新疆地区汉族人群AD发病有关,ABCA7基因位点rs2075650、CD33基因位点rs3826656多态性在新疆地区维吾尔族与汉族AD患者中存在差异。

Background Genome-wide association analysis(GWAS)revealed that,there are multiple Alzheimer's disease(AD)related susceptibility genes on Chr19.To intensively explore the pathogenesis and treatment of AD,it is essential to study polymorphisms of these genes in different ethnic groups.Objective To compare the polymorphisms in AD-associated genes on Chr19 in Uygur and Han people with AD in Xinjiang.Methods Uygur and Han participants were enrolled from August 2016 to June 2018,including 131 cases with AD(case group)recruited from Clinical Neurological Center,the Second Affiliated Hospital of Xinjiang Medical University,and Urumqi Liudaowan Hospital and Changji People's Hospital,and 128 cases health examinees(control group)from the Second Affiliated Hospital of Xinjiang Medical University.The genotypes and alleles of SNPs rs3764650,rs2075650,rs3826656,rs3865444 and rs3745833 of ABCA7,TOMM40,CD33 and GALP genes were analyzed by PCR amplification and sequencing.The genotype and allele frequency of representative AD-associated genes on Chr19 were compared in Han or Uygur participants between control group and case group,as well as between Han and Uygur participants in case group.Results The genotype and allele frequency of rs3764650,rs2075650,rs3826656,rs3865444 and rs3745833 distributed in case group and control group conformed to Hardy-Weinberg equilibrium(P>0.05).There were no significant differences of genotype and allele frequency of rs3764650,rs2075650,rs3826656,rs3865444 and genotype frequency of rs3745833 in Han participants between control group and case group(P>0.05),but the allele frequency of rs3745833 differed significantly(P<0.05).There were no significant differences of genotype and allele frequency of rs3764650,rs2075650,rs3826656,rs3865444 and rs3745833 in Uygur participants between control group and case group(P>0.05).There were no significant differences of genotype and allele frequency of rs2075650,rs3865444 and rs3745833,as well as allele frequency of rs3826656 between Han and Uygur participants with AD(P>0.05),but the differences of genotype and allele frequency of rs3764650,as well as allele frequency of rs3826656 were significant(P<0.05).The linkage disequilibrium of CD33 gene rs3826656 and rs3865444 was found in Han,Uygur or AD participants.There were no significant differences in GC,AA and AC genotypes frequency of haplotypes of rs3826656-rs3865444 in Han or Uygur population between control group and case group(P>0.05).There was no significant difference in the GC and AA genotypes frequency of haplotypes of rs3826656-rs3865444 between Han and Uygur participants with AD(P>0.05).The AC genotype frequency of haplotypes of rs3826656-rs3865444 in Uygur AD participants was higher than that of Han AD participant(s P<0.05).Conclusion The rs3745833 polymorphism of GALP gene may be related to Han AD patients in Xinjiang.There are differences in rs2075650 and rs3826656 polymorphisms between Uygur and Han AD patients.