THRB基因第7、第10外显子遗传标记与抑郁症的关联和连锁不平衡研究

目的从单核苷酸多态性(SNP)和单倍型分析的角度入手分析抑郁症患者甲状腺激素β受体(THRB)基因与抑郁症之间的关系。方法入组抑郁症患者及健康对照者各50例,均为中国陕西籍汉族人。提取基因组DNA,对THRB基因第7、第10外显子测序,并对患者进行汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评分。测序结果进行序列比对,采用SPSS软件进行统计分析,采用SHEsis在线分析系统、LDA 1.0软件、Haploview 4.0软件进行单倍型和连锁不平衡分析。结果全部样本THRB基因第7外显子上未发现SNP,抑郁症患者组第10外显子上发现G1457T和G1671A两处SNP,健康对照组第10外显子上发现G1671A一处SNP,组间分布无统计学差异(P>0.05)。THRB基因G1671A与G1457T两处SNP构成的单倍型位于存在强烈连锁不平衡关系的单倍型域内,抑郁症患者组中存在3种单倍型分布,表现为连锁不平衡关系;健康对照组中发现两种单倍型分布,不存在连锁不平衡关系。携带THRB基因G1671A杂合子的抑郁症患者HAMD量表总分高于野生型纯合子个体;携带THRB基因G1457T杂合子的抑郁症患者HAMD量表抑郁情绪、HAMA量表抑郁心境得分高于野生型纯合子个体,HAMD迟缓因子得分低于野生型纯合子个体。结论中国陕西省汉族抑郁症患者THRB基因第7、第10外显子上存在不同于现有报道的SNP分布,G1671A与G1457T两处SNP位点及其构成的单倍型与抑郁症不存在关联和连锁不平衡,携带THRB基因G1671A杂合子和/或携带THRB基因G1457T杂合子的抑郁症患者有不同于携带上述两位点野生型纯合子个体的临床表现型。

Association and linkage disequilibrium between depression and genetic markers on THRB gene exons 7 and 10

Objective To find the relationship between thyroid hormone receptor β(THRB) gene and depression with single nucleotide polymorphism(SNP) and haplotype analyses. Methods Blood samples were collected from 50 depression patients and 50 healthy controls of Shaanxi Han nationalities;exon-7 and exon-10 of THRB gene of all the samples were sequenced.HAMD and HAMA were scaled in patients;haplotype and linkage disequilibrium analyses were made with SPSS 13.0,BLAST online,SHEsis online,LDA 1.0,and Haploview 4.0. Results No SNP was found on exon-7 of all the 100 samples.Two SNPs G1457T and G1671A were found in exon 10 in the patient group,and one SNP G1671A was found on exon-10 in the control group.However,no significant difference was found between the two groups before or after stratification(P>0.05).The haplotypes combined with G1457T and G1671A were located in a block with strong linkage disequilibrium with other blocks.Three haplotypes were found in the patient group,which showed linkage disequilibrium while two haplotypes were found in the control group which showed no linkage disequilibrium.Patients with G1671A heterozygote showed a higher sum of HAMD than the ones with wild type homozygote;patients with G1457T heterozygote showed higher scores of depressive mood in HAMD and HAMA,and lower scores of retardation factor of HAMD than the ones with wild type homozygote. Conclusion Shaanxi Chinese Han depression patients have different distributions of SNPs on exon-7 and exon-10 of thyroid hormone receptor β gene,compared with other reports.There is no association and linkage disequilibrium between depression and THRB gene G1457T and G1671A SNPs and haplotypes.Depression patients with THRB gene G1457T and/or G1671A heterozygotes show different clinical manifestations compared with the ones with homozygotes.