Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Am J Hum Genet. 2011 May 13;88(5):664-73. doi: 10.1016/j.ajhg.2011.04.015.
Thyroid disorders such as goiters represent important diseases, especially in iodine-deficient areas. Sibling studies have demonstrated that genetic factors substantially contribute to the interindividual variation of thyroid volume. We performed a genome-wide association study of this phenotype by analyzing a discovery cohort consisting of 3620 participants of the Study of Health in Pomerania (SHIP). Four genetic loci were associated with thyroid volume on a genome-wide level of significance. Of these, two independent loci are located upstream of and within CAPZB, which encodes the β subunit of the barbed-end F-actin binding protein that modulates actin polymerization, a process crucial in the colloid engulfment during thyroglobulin mobilization in the thyroid. The third locus marks FGF7, which encodes fibroblast growth factor 7. Members of this protein family have been discussed as putative signal molecules involved in the regulation of thyroid development. The fourth locus represents a "gene desert" on chromosome 16q23, located directly downstream of the predicted coding sequence LOC440389, which, however, had already been removed from the NCBI database as a result of the standard genome annotation processing at the time that this study was initiated. Experimental proof of the formerly predicted mature mRNA, however, demonstrates that LOC440389 indeed represents a real gene. All four associations were replicated in an independent sample of 1290 participants of the KORA study. These results increase the knowledge about genetic factors and physiological mechanisms influencing thyroid volume.
甲状腺疾病，如甲状腺肿，是一种重要的疾病，特别是在碘缺乏地区。同胞研究表明，遗传因素对甲状腺体积的个体间差异有很大影响。我们通过分析波罗的海健康研究（SHIP）中 3620 名参与者的发现队列，对该表型进行了全基因组关联研究。在全基因组水平上，有四个遗传位点与甲状腺体积相关。其中，两个独立的位点位于 CAPZB 的上游和内部，CAPZB 编码了肌动蛋白聚合的调节因子，即丝状肌动蛋白结合蛋白的β亚基，这一过程对甲状腺球蛋白动员过程中胶体的吞噬至关重要。第三个位点标记了 FGF7，它编码成纤维细胞生长因子 7。该蛋白家族的成员被认为是参与甲状腺发育调节的假定信号分子。第四个位点代表 16q23 上的一个“基因荒漠”，位于预测编码序列 LOC440389 的直接下游，然而，由于在本研究启动时对标准基因组注释处理，该基因已从 NCBI 数据库中删除。然而，以前预测的成熟 mRNA 的实验证明，LOC440389 确实代表了一个真正的基因。这四个关联在 KORA 研究的 1290 名参与者的独立样本中得到了复制。这些结果增加了我们对影响甲状腺体积的遗传因素和生理机制的认识。
