HD基因和UCHL-1基因多态性与Huntington病关系的研究  

HD and UCHL-1 genotype analysis in Huntington's disease

作　　者：许二赫[1] 李丹[1] 贾建平[1] 

机构地区：[1]首都医科大学宣武医院神经内科,北京100053

出　　处：《中国神经精神疾病杂志》2007年第7期395-399,共5页Chinese Journal of Nervous and Mental Diseases

摘　　要：目的探讨Huntington病患者发病年龄与HD基因和UCHL-1基因S18Y多态性相关情况。方法应用聚合酶链式反应(polymerase chain reaction,PCR)技术检测两个HD家系(53人)、6例非家系HD患者和51名正常对照组HD基因CAG重复次数;应用聚合酶链式反应-限制性内切酶分析(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术检测UCHL-1基因S18Y多态性的分布情况。结果在两个家系中确诊了5例HD病人,在其有高度遗传风险的子女中发现4例症状前患者。UCHL-1基因S18Y多态性的基因型和等位基因分布频率在两个家系和正常对照组中无统计学差异(SY型基因型在三种基因型中最常见,频率>50%)。非家系患者中未见YY基因型,SS基因型多于SY型,S等位基因多于Y型,与正常对照组差别有统计学意义。多元线性回归研究显示11例病人发病年龄变异的15.6%是由其UCHL-1基因S18Y多态性造成的。CAG重复次数可解释发病年龄变异的71.4%。结论HD基因CAG重复次数是决定患者发病年龄变异的最主要因素,但不是唯一因素。UCHL-1基因S18Y多态性是HD的调节基因,对发病年龄有微弱的调节作用,提示UCHL-1可能参与HD的发病机制。Objective To study the CAG trinucleotide repeats and the polymorphisms of ubiquitin carboxy-termihal hydrolase L1 （UCHL-I） gene SISY in clinical diagnosed HD patients in two kindreds, and to explore their relationships to the age of onset in HD patients. Methods CAG trinucleotide repeats and UCHL-I SISY polymorphisms were determined using PCR and PCR-RFLP in subjects of two HD kindreds, 6 unrelated HD patients and 51 healthy controls. Results Among the two kindred 5 patients who have been diagnosed HD clinically were ascertained by genetic test. There are other 4 presymptomatic patients in high-risk families. Analysis showed no significant difference between kindreds and controls for genotype or allele frequencies of the UCHL-1 S18Y polymorphisms with SY genotype which the most common genotype. But contrast to it of related HD group, the distribution difference of the unrelated HD patients who have no YY genotype is statistically lignificat multiple linear regression analysis revealed that variations in CAG repeats and UCHL-I gene S18Y polymorphism account for 71.4% and 15.6% , respectively, of the total variance in the AO of the 11 HD patients. Conclusions A remarkable characteristic of HD CAG trinucleotide repeat is that they undergo dynamic mutations in which repeat number may increase dramatically when it is transmitted from an uneffected parent with a mutant allele to the offspring, this data demonstrated that variations in UCHL-1 S18Y polymorphisms may be a genetic factor that influences the variability in HD age of onset. Although the effect may be modest, it can be important in disease pathogenesis and may provide a target for neuroprotective strategy in HD.

关 键 词：HUNTINGTON病 发病年龄 CAG重复序列 UCHL-1基因 S18Y多态性 

分 类 号：R742.2[医药卫生—神经病学与精神病学]