Huang Q, Parfitt A, Grennan D M, Manolios N
Department of Rheumatology, Royal North Shore Hospital St. Leonards, NSW, Australia.
Autoimmunity. 1997;26(2):85-93. doi: 10.3109/08916939709003851.
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.
我们检验了一个假说，即同卵（MZ）双胞胎中系统性红斑狼疮（SLE）的低一致性率可能是由X染色体失活的差异所导致的。招募了五对MZ双胞胎，其中四对不一致，一对一致，通过DNA指纹图谱确认了合子性，并检查了从外周血和颊细胞制备的DNA样本中他们的X染色体失活模式。在用甲基化敏感酶HpaII或HhaI消化并进行PCR扩增后，通过X染色体上雄激素受体基因外显子1中三核苷酸重复序列附近的CpG区域的甲基化状态来评估X染色体失活。在所有四对不一致的双胞胎对中，发现受影响和未受影响的双胞胎之间的X染色体失活模式相同，两对为随机模式，另外两对为偏斜模式。一致的双胞胎表现出相同的随机模式。还从颊涂片DNA中检查了X染色体失活情况，并且在一对信息丰富的双胞胎对中显示出与外周血DNA中观察到的模式相同。在这五对MZ双胞胎对中未观察到X染色体失活模式的差异。这些结果不支持X染色体失活差异是导致SLE的MZ双胞胎中一致性率低的机制这一假说。
