Genotype-Based Epigenetic Differences in Monozygotic Twins Discordant for Positive Antithyroglobulin Autoantibodies
Genotype-Based Epigenetic Differences in Monozygotic Twins Discordant for Positive Antithyroglobulin Autoantibodies
复制标题
抗甲状腺球蛋白自身抗体阳性的同卵双胞胎中基于基因型的表观遗传差异
DOI：
10.1089/thy.2017.0273
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发表时间：
2018
期刊：
影响因子：
6.6
通讯作者：
Iwatani Yoshinori
中科院分区：
文献类型：
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作者：
Watanabe Mikio;Takenaka Yoichi;Honda Chika;Osaka Twin Research Group;Iwatani Yoshinori
背景：与自身免疫性疾病发展相关的表观遗传因素尚不清楚。抗甲状腺球蛋白自身抗体（TgAb）阳性不一致的同卵双生子对由于其相同的遗传背景，可用于检查表观遗传因素。本研究的目的是澄清不和谐的表观遗传差异影响的发展TgAb.Methods：主题是从257日本单卵双胞胎，招募从登记处建立的双胞胎研究中心在大坂大学。TgAb阳性一致（PC）对分别为5.7%（4对）和9.6%（18对）的男性和女性对。TgAb不一致（DC）对分别为11.4%（8对）和8.0%（15对）的男性和女性对。TgAb阴性一致（NC）对占男性对的78.6%（55对）和女性对的74.3%（139对）。为了进行更严格的分组，将阳性TgAb的临界值设定为50.0 IU/mL（TgAb阴性：<28.0 IU/mL; TgAb阳性：≥50.0 IU/mL; TgAb临界值：≥28.0 IU/mL且<50.0 IU/mL）。最终检查了TgAb阳性的19个不一致对（6个男性和13个女性对）和185个一致对（48个男性和137个女性对）。使用Infinium HumanMethylation 450 BeadChip试剂盒评价基因组DNA的DNA甲基化水平。基因多态性也进行了基因分型，使用Omni 5 -4 BeadChip试剂盒，以澄清特定的遗传背景不一致twin.Results：没有发现CpG位点与TgAb DC对校正后的多重比较的甲基化水平显着的对内差异。然而，155个TgAb DC对特异性多态性的基因型频率显着不同的一致对，他们都没有位于6号染色体的HLA区域。在TgAb DC对这些多态性的一些特定的基因型，四个CpG位点被观察到表现出显着的对内差异，在每个DC对，即使校正后的多重comparation.Conclusions：本研究发现，TgAb DC双胞胎谁是容易表观遗传变化的特定的遗传背景是不同的TgAb PC双胞胎，它澄清了基于基因型的表观遗传差异TgAb DC单卵双胞胎。
Background:Epigenetic factors associated with the development of autoimmune diseases are unclear. Monozygotic twin pairs discordant for positive antithyroglobulin autoantibodies (TgAb) are useful to examine the epigenetic factors because of their identical genetic background. This study aimed to clarify the discordant epigenetic differences affecting the development of TgAb.Methods:Subjects were selected from 257 Japanese monozygotic twins, recruited from the registry established by the Center for Twin Research at Osaka University. TgAb positive concordant (PC) pairs were 5.7% (four pairs) and 9.6% (18 pairs) of male and female pairs, respectively. TgAb discordant (DC) pairs were 11.4% (eight pairs) and 8.0% (15 pairs) of male and female pairs, respectively. TgAb negative concordant (NC) pairs were 78.6% (55 pairs) of male pairs and 74.3% (139 pairs) of female pairs. To perform stricter grouping, the cut-off value for positive TgAb was set to 50.0 IU/mL (TgAb negative: <28.0 IU/mL; TgAb positive: ≥50.0 IU/mL; TgAb borderline: ≥28.0 IU/mL and <50.0 IU/mL). Nineteen discordant (6 male and 13 female pairs) and 185 concordant pairs (48 male and 137 female pairs) for TgAb positivity were finally examined. DNA methylation levels of genomic DNA were evaluated using the Infinium HumanMethylation450 BeadChip Kit. Gene polymorphisms were also genotyped using the Omni5-4 BeadChip Kit to clarify genetic background specific for discordant twins.Results:No CpG sites were found with significant within-pair differences of methylation levels in TgAb DC pairs after correction for multiple comparisons. However, 155 polymorphisms specific for TgAb DC pairs were significantly different in genotype frequencies from those of concordant pairs, and none of them were located on the HLA region of chromosome 6. In TgAb DC pairs with some specific genotypes of these polymorphisms, four CpG sites were observed exhibiting significant within-pair differences in each DC pair, even after correction for multiple comparisons.Conclusions:This study found that the genetic background specific for TgAb DC twins who are susceptible to epigenetic changes are different from that specific for TgAb PC twins, and it clarified the genotype-based epigenetic differences in TgAb DC monozygotic twins.