Ban Yoshiyuki, Greenberg David A, Davies Terry F, Jacobson Eric, Concepcion Erlinda, Tomer Yaron
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
J Clin Endocrinol Metab. 2008 Sep;93(9):3589-96. doi: 10.1210/jc.2008-0364. Epub 2008 Jun 17.
Epidemiological data suggest a genetic susceptibility to thyroid antibody (TAb) production.
The objective of the study was to identify genetic loci that are linked with TAb production.
The design of the study was a whole genome linkage study in families with clustering of thyroid autoimmunity.
The study took place at an academic medical center.
Participants included 102 multigenerational families (540 individuals) multiplex for autoimmune thyroid disease (AITD) and TAb production.
We computed two-point logarithm of odds (LOD) scores and multipoint heterogeneity LOD scores for 400 microsatellite markers spanning the entire human genome at an average distance of 10 cm (approximately 10 Mb).
Three loci showed evidence for linkage with TAb production: 1) 2q locus, which gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5), which was the same AITD-1 locus found to be linked with clinical AITD; and (3) 8q locus (HLOD 2.2), which contained the thyroglobulin gene, also previously reported to be linked and associated with AITD. All loci that were linked to TAb were also linked to AITD, suggesting that TAb and AITD share the same genetic predisposition.
We conclude that: 1) some of the genes/loci predisposing to TAb and AITD are shared, whereas distinct genes/loci also exist; (2) the presence of TAb in relatives of AITD patients may be associated with increased risk for the development of clinical AITD; and (3) further studies are needed to determine the predictive value of TAb levels for the development of clinical AITD in relatives of patients with familial AITD.
流行病学数据表明存在甲状腺抗体（TAb）产生的遗传易感性。
本研究的目的是确定与TAb产生相关的基因位点。
本研究的设计是对甲状腺自身免疫聚集的家族进行全基因组连锁研究。
研究在一家学术医疗中心进行。
参与者包括102个多代家族（540人），这些家族患有自身免疫性甲状腺疾病（AITD）且产生TAb。
我们计算了跨越整个人类基因组的400个微卫星标记的两点对数优势（LOD）分数和多点异质性LOD分数，平均距离为10厘摩（约10兆碱基）。
三个位点显示出与TAb产生相关的证据：1）2q位点，其最大多点异质性LOD分数（HLOD）为2.8，包含CTLA - 4基因，此前报道该基因与临床AITD相关联；（2）6p位点（HLOD 2.5），这是发现与临床AITD相关联的同一个AITD - 1位点；（3）8q位点（HLOD 2.2），其包含甲状腺球蛋白基因，此前也报道该基因与AITD相关联。所有与TAb相关的位点也与AITD相关联，这表明TAb和AITD具有相同的遗传易感性。
我们得出以下结论：1）一些导致TAb和AITD的基因/位点是共享的，但也存在不同的基因/位点；（2）AITD患者亲属中TAb的存在可能与临床AITD发生风险增加有关；（3）需要进一步研究以确定TAb水平对家族性AITD患者亲属中临床AITD发生的预测价值。
