X-Chromosome Inactivation in Monozygotic Twins with Systemic Lupus Erythematosus

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 Hpall or Hhal 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.