AANAT基因与青少年特发性脊柱侧凸的关联研究

目的 探讨人体内褪黑素合成通路与青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)发病之间的关系.方法 以单核苷酸多态性(SNP)位点为遗传标记,用测序法对性别(女性比率分别为77.67%和75.00%,P=0.648)和年龄[平均年龄分别为(15.18±2.15)岁和(15.58±2.50)岁,P=0.217]匹配的103例AIS患者和108例对照组进行基因分型筛查,对最小等位基冈频率(MAF)≥5%的位点结果 分别用SNPStats软件在线进行Hardy-Weinberg遗传平衡检验和单位点统计分析,用Unphased V3.07进行连锁不平衡(LD)检验和单倍体分析.结果 位于功能区的9个SNPs位点中只有rs28936679、rs4238989和rs3760138三个位点满足MAF≥5%,并满足Hardy-Weinberg遗传平衡检验;单位点分析结果 显示,5个Logistic回归分析模型检验的所有P值均＞0.05,提示这3个位点与AIS的发病无关;LD检验显示它们之间没有两个处在同一个单倍体块(D＞0.8)上,因而无法进行单倍体检验.结论 AANAT基因不是AIS的易感基因,我们需要对其他褪黑素合成相关的酶基因进行筛查研究.

Association study of arylalkylamine N-acetyrltransferase polymorphisms with adolescent idiopathic scoliosis

Objective To access whether arylalkylamine N-acetyltransferase(AANAT)polymorohisms is associated with the predisposition of adolescent idiopathic scoliosis(AIS),and study the relationship between the biosynthesis pathway of melatonin and the onset of AIS in Human.Methods We genotyped 9 reported single nuclear polymorphisms(SNPs)present in AANAT located in the functional regions by PCR-Sequence Analysis in 103 AIS patients and 108 controls with matched sex and age(Female:77.67%&75.00%.P=0.648;Mean age:15.18±2.15 & 15.58±2.50,P=0.217).The data of the SNPs with minor allele frequence (MAF)above 5%were analyzed by Hardy-Weinberg equilibrium test and single-SNP analysis with SNPStat.Linkage disequilibrium(LD)analysis and the haplotype analysis with Unphased v3.07.Resuits There were three SNPs of m28936679,rs4238989,and rs3760138 with MAF above 5%in all,and the distributions of the alleles of all the 3 SNPs met Hardy-Weinberg equilibrium in the samples.The single-SNP analysis showed none of them was related with the occurrence of AIS:in Codominant model.the P values of rs28936679.rs4238989 and rs3760138 were 0.86,0.65 and 0.14 respectively;in Dominant model,the P values were 0.96.0.40 and 0.14 respectively;in Recessive model,the P values were 0.59,0.94 and 0.08 respectively:in Overdominant model,the P values were 0.89,0.41 and 0.60 respectively;and in Log-additive model.the P values were 0.84,0.62 and 0.06 respectively.All 3 SNPs in AANAT were shown in "weak LD"(rs28936679-rs4238989:D'=0.506;rs28936679-rs3760138:D'=0.210;rs4238989-rs3760138:D'=0.756:and rs28936679-rs4238989-rs37601 38:D'=0.451),and there was no LD block(D'＞0.8)among them,so we couldn't make the haplotype analysis.Conclusion These resuhs suggested that AANAT might not be a predisposition gene of AIS,and we should pay more attention to other related genes in the biosynthesis pathway of melatonin.