胃泌素释放肽受体基因多态性与儿童孤独症的关联研究

Research on childhood autism and gastrin-releasing peptide receptor gene polymorphism

目的探讨胃泌素释放肽受体(GRPR)基因第二外显子1106C/T和1316C/T单核苷酸多态性(SNP)在西安市汉族儿童中的分布特征及与孤独症(CA)的关系。方法采用聚合酶连反应(PCR)技术,对59例孤独症患儿、82名正常对照儿童的2个SNP位点的基因型进行检测,通过测序进行验证。用病例-对照和传递不平衡检验(TDT)分析SNP位点等位基因的分布,并对2个SNP位点的连锁、单体型及与孤独症行为的表现进行分析。结果①CA组和正常对照组GRPR基因第二个外显子1106和1316位点均有多态性表现,以TT基因型为主,未发现其他多态性位点。其中正常对照组儿童TT、TC、CC三基因型频率分别为68.3%、17.1%和14.6%,CA组分别为67.8%、16.9%和15.3%,各自按Hardy-Weinberg平衡温和度检验,差异无统计学意义(χ2=3.81、4.52,P均>0.05)。两组基因型频率和等位基因频率分布差异无统计学意义(χ2=0.01、0.24,P均>0.05)。②CA组儿童性别间基因型分布和等位基因分布差异无统计学意义(χ2=4.96、2.37,P均>0.05);正常对照组男女间TT、CT基因型分布差异有统计学意义(χ2=6.64,P<0.05),两组等位基因分布差异无统计学意义(χ2=2.04,P>0.05)。③经秩相关性分析各基因型与描述儿童孤独症行为的ABC量表的总分和各因子分无相关性(rs=0.010～0.145,P均>0.05)。结论西安市汉族儿童中GRPR基因第二个外显子1106和1316位点存在基因多态性,并以TT基因型为主。未发现孤独症患儿和正常儿童间GRPR基因第二个外显子1106和1316基因多态性存在差异。正常对照儿童性别间TT、TC两组等位基因间存在差异。ABC量表的总分和各因子分与该基因多态性无相关性。

Objectives To investigate the characteristics of distribution on single nucleotide polymorphisms （SNP） of the exon-2 in human gastrin-releasing peptide receptor （GRPR） gene 1106 C/T and 1316 C/T in children of the Chinese Han ethnic group in Xi＇an, and its association with autism. Methods Fifty-nine （59） autism children and 82 normal children were included. Genotypes of 2 SNP loci in all enrolled children were defined by polymerase chain reaction （PCR）, and confirmed by gene sequencing. The allele＇s frequencies of SNPs were analyzed with case-control study and transmission disequilibrium test （TDT） , linkage of the 2 loci and haplotype composed of the 2 loci were also studied. Results 1 ） Polymorphism of sites of 1 106 and 1 316 in exon-2 GRPR gene was present in all subjects. The frequency of each genotype was 68.3% （TT）, 17.1% （TC） and 14.6% （CC） in normal Xi＇an children, and 67.8% （TT）, 16.9% （TC） and 15.3% （CC） in childhood autism （CA） group （χ2 = 0.01, P 〉 0.05）. No significant difference was found in distribution of GRPR in 1 106 and 1 316 according to Hardy-Weinberg principle statistics between normal group and CA group （χ2 = 3.81, 4.52, P 〉 0.05）. 2） There are no significant difference in frequency of each genotype between boys and girls in CA （χ2 = 4.96, P 〉 0.05）. 3 ） There are significant difference in frequency of each genotype TT and CT between boys and girls in control group （χ2 = 6.64 , P 〈 0.05） ; No significant difference in frequency among each genotype on the scores of ABC scores in CA （rs = 0.010 - 0.145, P 〉 0.05）. Conclusions The polymorphism of sites of 1 106 and 1 316 in exon-2 GRPR gene was present in all subjects with more frequency of Tr genotype in both groups. There are significant difference in frequency of geuotype TT, CT between boys and girls in the control group. There were no significantly association between genotypes of the exon-2 GRPR gene and the score of ABC in CA.