TPO基因多态性与先天性甲状腺素合成障碍性甲低的关联分析

Association of thyroperoxidase gene polymorphisms with dyshormonogenesis in congenital hypothyroidism

目的探讨甲状腺过氧化物酶（thyroperoxidase，TPO）基因单核苷酸多态性（single nucleotide polymorphisms，SNP）与先天性甲状腺素合成障碍性甲低（congenital hypothyroidism，CH）的相关性。方法测序筛查30例随机无血缘关系个体的TPO基因17个外显子及两端侧翼部分的变异位点，选取用于与甲状腺素合成障碍性CH关联性研究的SNPs位点；以136例甲状腺素合成障碍性CH患儿为病例组，相同地区的141名健康儿童为对照组，应用PCR-直接测序法或PCR-限制性片段长度多态性（restriction fragment length polymorphism，RELP）方法分析所选取的SNPs位点基因型。结果基因筛查发现8个位于外显子区域SNPs位点，选择rs9678281、rs376413622、rs1126797、rs4927611、rs732609和rs1126799这6个sNPs为研究位点；rs4927611和rs732609等位基因频率和基因型频率在病例组和对照组间的差异有统计学意义（P〈0．05）；在隐性模式下，病例组rs4927611TT基因型（OR=0．32，95％CI：0．112～0．915，P=0．047）和rs732609CC基因型（OR=0．484，95％CI：0．253～0．927，P=0．04）频率显著高于对照组。结论丁PO基因rs4927611和rs732609位点多态性与甲状腺素合成障碍性CH的发生密切相关；rs4927611TT基因型和rs732609CC基因型可能是先天性甲状腺功能低下症的潜在危险因素。

Objective To assess the association of thyroperoxidase （TPO） gene polymorphisms with dyshormonogenesis in congenital hypothyroidism （CH）. Methods The 17 exons and flanking introns of the TPO gene from 30 randomly selected samples were sequenced for the selection of single nueleotide polymorphisms （SNPs）. In 136 patients with dyshormonogenetic CH and 141 healthy controls from the same region, the selected SNPs were genotyped by polymerase chain reaction （PCR） and direct sequencing or PCR-restriction fragment length polymorphism （RFLP）. Results Six SNPs （rs9678281, rs376413622, rs1126797, rs4927611, rs732609 and rs1126799） were selected to determine the genotype for each sample. Among these, rs4927611 and rs732609 showed a significant difference between the two groups in both allelic and genotypic frequencies. With a recessive model of inheritance, rs732609 CC （OR= O. 484, 95%CI： 0. 25340. 927, P=0.04） and rs4927611 TT （OR=0.32, 95 %CI： 0. 112-0. 915, P=0. 047） were greater in the patients. Conclusion rs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.