X-chromosome inactivation in monozygotic twins with systemic lupus erythematosus
X-chromosome inactivation in monozygotic twins with systemic lupus erythematosus
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DOI：
10.3109/08916939709003851
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发表时间：
1997-01-01
期刊：
影响因子：
3.5
通讯作者：
Manolios, N
中科院分区：
文献类型：
--
作者：
Huang, QR;Parfitt, A;Manolios, N
系统性红斑狼疮 (SLE) 的同卵 (MZ) 双胞胎中的低一致性率可能是由于 X 染色体失活的差异造成的，这一假设得到了检验。招募了五对同卵双胞胎，其中四对不一致，一对一致，通过DNA指纹图谱确认接合性，并检查了从外周血和口腔细胞制备的DNA样本中X染色体失活的模式。 X 染色体失活通过用甲基化敏感酶 HpaII 或 HhaI 消化并 PCR 扩增后 X 染色体上雄激素受体基因外显子 1 中三核苷酸重复附近的 CpG 区域的甲基化状态来评估。在所有四对不一致的双胞胎中，发现受影响和未受影响的双胞胎之间的 X 染色体失活模式是相同的，其中两对是随机模式，其他对是倾斜模式。一致的双胞胎表现出相同的随机模式。还从口腔涂片 DNA 中检查了 X 染色体失活，结果显示其与一对信息丰富的双胞胎外周血 DNA 中观察到的 X 染色体失活模式相同。在这五对同卵双胞胎中没有观察到 X 染色体失活模式的差异。结果不能支持这样的假设：X 染色体失活的差异是导致患有 SLE 的同卵双胞胎中一致率较低的机制。
The hypothesis that a low concordance rate in monozygotic (MZ) twins with systemic lupus erythematosus (SLE) may be accounted for by differences in X-chromosome inactivation was examined. Five MZ twin pairs, four discordant and one concordant, were recruited, zygosity confirmed by DNA fingerprinting, and their pattern of X-chromosome inactivation in DNA samples prepared from peripheral blood and buccal cells were examined. X-chromosome inactivation was assessed by the methylation status of the CpG region near trinucleotide repeats in exon 1 of the androgen receptor gene on X-chromosome after digestion with the methylation-sensitive enzyme HpaII or HhaI and PCR amplification. X-chromosome inactivation patterns were found to be the same between affected and non-affected twins in all four discordant twin pairs, with random patterns in two pairs and skewed patterns in the others. The concordant twins demonstrated the same random patterns. X-chromosome inactivation was also examined from buccal smear DNA and shown to have the same pattern as that noted from peripheral blood DNA in one informative twin pair. Differences in X-chromosome inactivation patterns were not observed in these five MZ twin pairs. The results could not support the hypothesis that differences in X-chromosome inactivation is the mechanism accounting for the low concordance rate noted in MZ twins with SLE.