3 years ago

Genotype-based epigenetic differences in monozygotic twins discordant for positive anti-thyroglobulin autoantibodies.

Mikio Watanabe, Chika Honda, Yoichi Takenaka, Osaka Twin Research Group, Yoshinori Iwatani
Background: Epigenetic factors associated with the development of autoimmune diseases are unclear. Monozygotic twin pairs discordant for positive anti-thyroglobulin autoantibodies (TgAb) are useful to examine the epigenetic factors because of their identical genetic background. Purpose: To clarify the discordant epigenetic differences affecting the development of TgAb. Subjects: We selected subjects 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% (4 pairs) and 9.6% (18 pairs) of male and female pairs, respectively. TgAb discordant (DC) pairs were 11.4% (8 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, in this study, we set the cut-off value for positive TgAb to 50.0 IU/mL (TgAb Negative: <28.0IU/mL, TgAb Positive: >=50.0IU/mL. TgAb Borderline: =>28.0IU/mL and <50.0IU/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. Methods: We evaluated DNA methylation levels of genomic DNA using the Infinium HumanMethylation450 BeadChip Kit (Illumina). We also genotyped gene polymorphisms using the Omni5-4 BeadChip Kit (Illumina) to clarify genetic background specific for discordant twins. Results: We did not find any CpG sites 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 was located on the HLA region of chromosome 6. In TgAb DC pairs with some specific genotypes of these polymorphisms, we observed four CpG sites exhibiting significant within-pair differences in each DC pair, even after correction for multiple comparisons. Conclusions: We 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 clarified the genotype-based epigenetic differences in TgAb-DC monozygotic twins.

Publisher URL: http://doi.org/10.1089/thy.2017.0273

DOI: 10.1089/thy.2017.0273

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