淀粉样前体蛋白基因多态性与汉族儿童青少年双相情感障碍的关联研究

An association study between genetic polymorphism of APP gene and pediatric bipolar disorder of Han nationality

目的探究淀粉样前体蛋白(amyloid precursor protein,APP)基因多态性与汉族儿童青少年双相情感障碍(bipolar disorder,BD)之间关联,寻找合适的单核酸多态性(single nucleotide polymorphisms,SNP)位点,为提前诊断和干预儿童青少年BD提供参考。方法选择178例汉族儿童青少年BD患者(病例组)和178例正常儿童青少年(对照组),提取两组外周血基因组DNA,从APP基因上取4个SNP(single nucleotide polymorphisms)位点,采用LDR-PCR SNP基因分型方法对儿童青少年BD患者和正常儿童青少年进行SNP分析。SPSS 22.0分析两组基因型频率和等位基因频率的差异,并使用软件SHEsis进行连锁不平衡分析和单倍型分析。结果APP基因4个SNP位点的基因型频率及等位基因频率在病例组和对照组差异有统计学意义(P<0.05)。APP基因4个SNP位点rs2040273、rs466433、rs463946、rs364048与BD相关联,差异有统计学意义(P<0.05)。构建4个SNP单倍型表明AACT、AGGC、GACT占总数的80%以上,单倍型中AGGC在病例组中所占百分比(11.9%)高于对照组(4.7%),差异有统计学意义(P<0.05),而且AGGC单倍体的关联比值比为2.727。结论APP基因4个SNP位点rs2040273、rs466433、rs463946、rs364048以及AGGC单倍型与汉族儿童青少年BD关联,APP基因是BD易感基因之一。

Objective To explore the association between genetic polymorphism of APP gene and bipolar disorder(BD)in children and adolescents for seeking suitable single nucleotide loci(SNP),and provide reference for early diagnosis and intervention of children and adolescent BD.Methods The genomic DNA of peripheral blood was extracted from 178 BD cases(case group)and 178 normal controls(control group)of Han children and adolescents.Four SNP loci of APP gene were selected and were analyzed by LDR-PCR SNP genotyping.Genotypes and allele differences were compared between the cases and control group by SPSS22.0 software.The software SHEsis was also used to make linkage disequilibrium and haplotype analysis.Results The genotype frequency and allele frequency of the 4 SNP loci of APP gene were statistically significant different between the case group and the control group(P<0.05).The association of s2040273,rs466433,rs463946,rs364048 with BD in the APP gene was statistically significant(P<0.05).The construction of 4 SNP haplotypes indicated that AACT,AGGC,and GACT accounted for more than 80%of the total.The percentage of haplotype AGGC in the case group(11.9%)was significantly higher than that in the control group(4.7%)(P<0.05),and the odds ratio of AGGC haploid was 2.727.Conclusion Four SNP loci s2040273,rs466433,rs463946,rs364048 in the APP gene and haplotype AGGC are associated with BD in Han children and adolescents.These results confirmed that the APP gene is one of BD susceptible gene.