妊娠期甲状腺功能减退相关基因分析  

Analysis of genes related to hypothyroidism during pregnancy

作　　者：梁琳 毛滢[2] 张俊荣 张思辰[2] 杨慧霞[1] Liang Lin;Mao Ying;Zhang Junrong;Zhang Sichen;Yang Huixia(Department of Obstetrics and Gynecology,Peking University First Hospital,Beijing 100034,China;Department of Obstetrics and Gynecology,Beijing Hospital,Beijing 100730,China)

机构地区：[1]北京大学第一医院妇产科,北京100034 [2]北京医院妇产科,北京100730

出　　处：《中华医学杂志》2019年第42期3350-3354,共5页National Medical Journal of China

摘　　要：目的通过比较分析甲状腺功能减退孕妇与正常对照组间单核苷酸多态性(SNP)的差异性位点,初步探索妊娠期甲状腺功能减退可能的致病机制.方法选取2018年1月至10月于北京医院分娩的妊娠期甲状腺功能减退孕妇,共53例;选择同期分娩并与病例组年龄匹配的正常对照组孕妇,共50名.应用Illumina ASA芯片对两组对象的血样本进行全基因组扫描,分析两组间差异显著性的SNP位点.查询人类基因组数据库hg19_dbsnp_version150,定位相关基因.分析相关基因与甲状腺功能异常及妊娠合并症的关联性.结果共发现了13个SNP位点:CERS6中的rs4668077(P=2.87E-05)、UGT1A1中的rs6717546(P=5.92E-05)、CASR中的rs1965358(P=7.78E-05)、CXCL14附近的rs916801(P=9.22E-05)、MAT2B附近的rs6886845(P=8.67E-05)、GRIK2中的rs76245053(P=2.07E-05)、HDAC9中的rs6977642(P=2.10E-05)、ATXN7L1附近的rs6949597(P=3.68E-05)、HTR7中的rs11186331(P=2.08E-05)、FBXO33附近的rs2415551(P=4.53E-05)、MIR4527中的rs75850124(P=9.24E-05)、rs76519339(P=9.24E-05)及CBX6附近的rs1014971(P=3.24E-05)在甲状腺功能减退组与对照组比较差异有统计学意义.结论相关基因中UGT1A1与甲状腺素在肝脏中代谢相关,CASR、CXCL14及CBX6与生殖能力相关,CXCL14、CASR、HBAC9及CERS6与代谢综合征相关,GRIK2、HTR7及FBOX33与神经精神疾病相关.妊娠期血清甲状腺素水平异常可能与UGT1A1变异引起的甲状腺素异常代谢相关.与生殖、代谢、神经精神疾病相关的基因提示,甲状腺功能减退与不孕、代谢综合征及神经精神类疾病间可能存在有连锁关系的致病基因.Objective By comparing and analyzing the differential sites of single nucleotide polymorphisms(SNP)between pregnant women with hypothyroidism and normal controls,the possible pathogenesis of hypothyroidism during pregnancy was explored.Methods A total of 53 pregnant women with hypothyroidism during pregnancy from January 2018 to October 2018 were enrolled.A total of 50 pregnant women who underwent concurrent delivery and matched age with the case group were selected.Whole blood scans were performed on blood samples from two groups of subjects using the Illumina ASA chip to analyze the SNP with significant differences between the two groups.The human genome database hg19_dbsnp_version150 was employed to locate related genes.The association of related genes with thyroid dysfunction and pregnancy complications were analyzed.Results A total of 13 SNPs were found in the study:rs4668077(P=2.87E-05)in CERS6,rs6717546(P=5.92E-05)in UGT1A1,rs1965358(P=7.78E-05)in CASR,rs916801(P=9.22E-05)near CXCL14,rs6886845(P=8.67E-05)near MAT2B,rs76245053 in GRIK2(P=2.07E-05),rs6977642(P=2.10E-05)in HDAC9,rs6949597(P=3.68E-05)near ATXN7L1,rs11186331(P=2.08E-05)in HTR7,rs2415551(P=4.53E-05)near FBXO33,rs75850124(P=9.24E-05)and rs76519339(P=9.24E-05)in MIR4527,rs1014971(P=3.24E-05)near CBX6 were statistically significant in the hypothyroidism group compared with the control group.Conclusions The related gene UGT1A1 is related to the metabolism of thyroxine in the liver.CASR,CXCL14 and CBX6 are related to reproductive ability.CXCL14,CASR,HBAC9 and CERS6 are related to metabolic syndrome,and GRIK2,HTR7 and FBOX33 are related to neuropsychiatric diseases.Abnormal serum thyroxine levels during pregnancy may be associated with abnormal metabolism of thyroxine caused by UGT1A1 mutation.Genes associated with reproduction,metabolism,and neuropsychiatric disorders suggest a pathogenic link between hypothyroidism and infertility,metabolic syndrome,and neuropsychiatric disorders.

关 键 词：妊娠 甲状腺功能减退 基因 单核苷酸多态性 

分 类 号：R71[医药卫生—妇产科学]