儿童和青少年桥本甲状腺炎的基因组学和表型组学：来自印度南部的一项前瞻性研究。
Genomics and phenomics of Hashimoto's thyroiditis in children and adolescents: a prospective study from Southern India.
机构信息
1 Department of Biochemistry, Mediciti Institute of Medical Sciences, Hyderabad, India ; 2 Endocrine Surgery, Endocare Hospital, Vijayawada, India ; 3 Department of Anatomy, Mediciti Institute of Medical Sciences, Hyderabad, India ; 4 Endocare Hospital, Vijayawada, India ; 5 Saveetha University, Chennai, India.
出版信息
Ann Transl Med. 2015 Nov;3(19):280. doi: 10.3978/j.issn.2305-5839.2015.10.46.
BACKGROUND
Hashimoto's thyroiditis (HT) is the commonest cause of acquired hypothyroidism in children and adolescents in iodine non-endemic areas. The genetic analysis in HT shows two types of susceptibility genes-immune regulatory and thyroid specific genes. The exact genotype-phenotypic correlations and risk categorization of hypothyroid phenotypes resulting from these known mutations are largely speculative. The genetic studies in pediatric HT are very sparse from Indian sub-continent. In this context, we analysed the prevalence of TPO, NIS and DUOX2 gene mutations along with genotype-phenotype correlations in hypothyroid children with HT.
METHODS
This is inter-disciplinary study conducted by collaboration between a tertiary care endocrinology hospital, biochemistry department of a teaching medical institute and genetics lab. In this prospective study, we employed 8 sets of primers and screened for 142 known single nucleotide polymorphisms in TPO, NIS, DUOX2 genes. The subjects were children and adolescents with hypothyroidism due to HT. Congenital hypothyroidism, iodine deficiency and dyshormonogenetic hypothyroidism cases were excluded.
RESULTS
We detected 8 mutations in 7/20 (35%) children in the entire cohort (6 in NIS and 2 in TPO genes. No mutations were observed in DUOX2 gene. All our mutations were localized in introns and we found none in exons. Except for bi-allelic, synonymous polymorphism of TPO gene in child No. 18, all other mutations were heterozygous in nature. Genotype-phenotype correlations show that our mutations significantly expressed the presence of associated autoimmune manifestations and existence of family history. Clinical phenotypes of painful thyroiditis, severity of hypothyroidism and absence of goiter were statistically significant in the presence of these mutations. But, they could not reach significance on multivariate analysis.
CONCLUSIONS
NIS gene followed by TPO mutations appears to be most prevalent mutations in HT amongst South Indian children and these mutations significantly influenced phenotypic expressions such as severity of hypothyroidism, goiter, auto-immune manifestations and family history.
背景
桥本甲状腺炎（HT）是碘非地方性地区儿童和青少年获得性甲状腺功能减退症的最常见原因。HT 的遗传分析显示两种易感基因-免疫调节和甲状腺特异性基因。这些已知突变导致的甲状腺功能减退表型的确切基因型-表型相关性和风险分类在很大程度上仍存在推测。来自印度次大陆的儿科 HT 遗传研究非常稀少。在这种情况下，我们分析了 HT 伴甲状腺功能减退症儿童中 TPO、NIS 和 DUOX2 基因突变的流行情况以及基因型-表型相关性。
方法
这是一项由三级保健内分泌医院、教学医学研究所的生化系和遗传实验室合作进行的跨学科研究。在这项前瞻性研究中，我们使用了 8 组引物，筛选了 TPO、NIS、DUOX2 基因中的 142 个已知单核苷酸多态性。研究对象为 HT 导致甲状腺功能减退的儿童和青少年。排除先天性甲状腺功能减退症、碘缺乏症和发育性甲状腺功能减退症病例。
结果
在整个队列的 20 名（35%）儿童中，我们检测到 8 个突变（6 个在 NIS 基因中，2 个在 TPO 基因中）。在 DUOX2 基因中未观察到突变。我们所有的突变都定位于内含子中，没有发现外显子中的突变。除了第 18 号患儿 TPO 基因的双等位基因同义多态性外，所有其他突变均为杂合性。基因型-表型相关性显示，我们的突变显著表达了相关自身免疫表现和家族史的存在。存在这些突变时，疼痛性甲状腺炎的临床表型、甲状腺功能减退的严重程度和无甲状腺肿均具有统计学意义。但在多变量分析中未达到显著性。
结论
NIS 基因紧随 TPO 突变之后，似乎是南印度儿童 HT 中最常见的突变，这些突变显著影响了甲状腺功能减退症的严重程度、甲状腺肿、自身免疫表现和家族史等表型表达。
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