Department of Endocrinology and Metabolism, Instituite of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Med Sci Monit. 2019 Feb 23;25:1439-1451. doi: 10.12659/MSM.911489.
BACKGROUND This study aimed to investigate susceptibility to Graves's disease and the association with the 5q32-33.1 region on chromosome 5 in a Chinese Han population. MATERIAL AND METHODS Eighty Chinese Han multiplex families included first-degree and second-degree relatives with Graves' disease. Eight microsatellite markers on chromosome 5 at the 5q32-33.1 region underwent linkage analysis and the association between the regions D5S1480-D5S2014 were studied. RESULTS The maximal heterogeneity logarithm of the odds (HLOD) score of D5S2090 was 4.29 (α=0.42) and of D5S2014 was 4.01 (α=0.34). A nonparametric linkage (NPL) score of 3.14 (P<0.001) was found for D5S2014. The D5S1480-D5S2014 region on chromosome 5 was associated with Graves' disease, with eight haplotype domains. There were significant differences in the sixth and eighth haplotype domains between patients with Graves' disease compared with normal individuals. Tagging single nucleotide polymorphisms (SNPs) of the sixth and eighth haplotype domains showed that individuals with SNP62 (rs12653715 G/C) who were GG homozygous had a significantly increased risk of Graves' disease compared GC heterozygous or CC homozygous individuals. The transmission disequilibrium test (TDT) indicated that SNP62 (rs12653715) and SNP63 (rs12653081) loci in the Janus kinase and microtubule interacting protein 2 (JAKMIP2) gene showed dominant transmission from heterozygous parents to the affected offspring, and SNPs in the secretoglobin family 3A member 2 (SCGB3A2) gene showed no transmission disequilibrium. The haplotype JAKMIP2-1 was identified as being particularly significant. CONCLUSIONS JAKMIP2 gene polymorphism require further study as potential risk factors for Graves' disease in the Chinese Han population.
本研究旨在探讨中国汉族人群 Graves 病的易感性及其与染色体 5q32-33.1 区域的相关性。
80 个中国汉族多因子家系包括 Graves 病的一级和二级亲属。对染色体 5q32-33.1 区域的 8 个微卫星标记物进行连锁分析，并研究了 D5S1480-D5S2014 区域之间的关联。
D5S2090 的最大异质对数似然比（HLOD）得分为 4.29（α=0.42），D5S2014 的 HLOD 得分为 4.01（α=0.34）。D5S2014 的非参数连锁（NPL）得分为 3.14（P<0.001）。染色体 5 的 D5S1480-D5S2014 区域与 Graves 病相关，存在 8 个单倍型域。与正常个体相比，Graves 病患者在第六和第八个单倍型域存在显著差异。第六和第八个单倍型域的标签单核苷酸多态性（SNP）显示，SNP62（rs12653715 G/C）中 GG 纯合子个体与 GC 杂合子或 CC 纯合子个体相比，患 Graves 病的风险显著增加。传递不平衡检验（TDT）表明，Janus 激酶和微管相互作用蛋白 2（JAKMIP2）基因中的 SNP62（rs12653715）和 SNP63（rs12653081）位点从杂合子父母向患病子女呈显性传递，而 secretoglobin family 3A member 2（SCGB3A2）基因中的 SNP 则无传递不平衡。JAKMIP2-1 单倍型被确定为特别显著。
JAKMIP2 基因多态性需要进一步研究，以确定其是否为中国汉族人群 Graves 病的潜在危险因素。
