Department of Twins Research and Genetic Epidemiology, Kings College London, London, United Kingdom.
PLoS One. 2013 Dec 6;8(12):e82558. doi: 10.1371/journal.pone.0082558. eCollection 2013.
To determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans.
76 N-glycan traits in circulating IgG were analyzed by UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip.
51 of the 76 glycan traits studied have an additive genetic component (heritability, h (2) ) ≥ 0.5. In contrast, 12 glycan traits had a low genetic contribution (h(2)<0.35). We then tested for association between methylation levels and glycan levels (P<2 x10(-6)). Among glycan traits with low heritability probe cg08392591 maps to a CpG island 5' from the ANKRD11 gene, a p53 activator on chromosome 16. Probe cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and particularly in regulation of splicing of mRNA precursors upon heat shock. Among those with high heritability we found cg13782134 (mapping to the NRN1L gene) and cg16029957 mapping near the QPCT gene to be array-wide significant. The proportion of array-wide epigenetic associations was significantly larger (P<0.005) among glycans with low heritability (42%) than in those with high heritability (6.2%).
Glycome analyses might provide a useful integration of genetic and non-genetic factors to further our understanding of the role of glycosylation in both normal physiology and disease.
确定遗传和表观遗传因素在多大程度上导致人类免疫球蛋白 G（IgG）糖基化的变化。
在来自 TwinsUK 的 220 对同卵双胞胎和 310 对异卵双胞胎中，通过 UPLC 分析了循环 IgG 中的 76 个 N-聚糖特征。使用经典的双胞胎研究设计，得出了定义这些特征变异的加性遗传、共同和独特环境成分。使用 Illumina 27k 芯片进行全基因组关联分析。
在所研究的 76 种糖基化特征中，有 51 种具有加性遗传成分（遗传率，h (2)）≥0.5。相比之下，有 12 种糖基化特征的遗传贡献较低（h (2)<0.35）。然后，我们测试了甲基化水平与糖基化水平之间的关联（P<2 x10(-6)）。在遗传率较低的糖基化特征中，探针 cg08392591 映射到染色体 16 上的 p53 激活因子ANKRD11 基因的 5'端的一个 CpG 岛。探针 cg26991199 映射到参与 RNA 剪接调节的 SRSF10 基因，特别是在热休克时调节 mRNA 前体的剪接。在遗传率较高的那些中，我们发现 cg13782134（映射到 NRN1L 基因）和 cg16029957 映射到 QPCT 基因附近的基因在数组范围内具有显著意义。在遗传率较低的糖基化特征中，与遗传率较高的糖基化特征（6.2%）相比，全基因组范围内的表观遗传关联比例明显更大（P<0.005）（42%）。
糖组分析可能为遗传和非遗传因素的综合提供有用的方法，以进一步了解糖基化在正常生理和疾病中的作用。
