褪黑素合成酶ASMT基因启动子和第一外显区单核苷酸多态性与儿童孤独症的关联研究

目的探讨参与褪黑素合成的乙酰血清素甲基转移酶(acetylserotonin methyltransferase,ASMT)基因启动子和第1外显子区遗传多态性位点与儿童孤独症是否关联。方法对390例儿童孤独症患者和420例正常对照者的ASMT基因启动子和第1外显子区域进行测序。比较该区域5个单核苷酸多态性(single nucl-eotide polymorphisms,SNPs)位点的等位基因频率、基因型频率和单体型频率在患者组与对照组之间的差异。结果患者组和对照组之间,5个SNPs(rs4446909、rs5989681、rs56690322、rs6644635、rs17149149)等位基因和基因型频率的差异均无统计学意义(P>0.05)。3个SNPs位点rs4446909、rs5989681和rs6644635之间存在连锁不平衡(linkage disequilibrium,LD)(D’值为0.85-0.98)。但此3个SNPs构成的单体型频率在两组间的差异无统计学意义(P>0.05)。结论本研究未发现ASMT基因启动子和第1外显子区域的遗传多态性位点与儿童孤独症关联,提示这些位点可能未参与中国汉族人群孤独症的致病。

Association study between polymorphisms in the promoter and exon 1 of ASMT and autism in a Chinese Han population.

Objective To investigate whether single nucleotide polymorphisms(SNPs) in ASMT(acetylserotonin methyltransferase) promotor and exon 1 were associated with autism in a Chinese Han population.Methods The polymorphisms in promoter and exon 1 were genotyped by direct sequencing in 390 Chinese Han individuals with autism and 420 healthy controls.Allele and genotype frequencies for each polymorphism were compared between patients and controls using Person’s chi-square analysis.Results our study did not detect significant differences of genotypic distribution and allele frequencies of 5 SNPs(rs4446909,rs5989681,rs56690322,rs6644635,and rs17149149) between autism patients and healthy controls(P > 0.05).Rs4446909,rs5989681,and rs6644635 were in one linkage disequilibrium(LD) block with D’ ranged from 0.85 to 0.98.However,the haplotypes constructed by these three SNP were not significantly associated with autism(P > 0.05).Conclusions Genetic variants in the pro-moter,and exon 1 of ASMT may be not significantly associated with autism in Chinese Han population.Further sequencing the other exons is needed.