Primary biliary cirrhosis in monozygotic and dizygotic twins: Genetics, epigenetics, and environment

Carlo Selmi, Marlyn J. Mayo, Nancy Bach, Hiromi Ishibashi, Pietro Invernizzi, Robert G. Gish, Stuart C. Gordon, Harlan I. Wright, Bruce Zweiban, Mauro Podda, M. Eric Gershwin

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346 Scopus citations

Abstract

Background & Aims: There is growing evidence that the interplay of genetic susceptibility and environmental factors leads to primary biliary cirrhosis (PBC). In particular, family members of an infected individual have up to a 100-fold higher risk of developing PBC. Although concordant rates for identical twins in other autoimmune diseases range between 25% and 50%, there are no such data on PBC. Accordingly, we evaluated the concordance of PBC in a genetically defined population of twin sets and evaluated the clinical characteristics between concordant subjects. Methods: We identified 16 pairs of twins within a 1400-family cohort followed up by several centers worldwide, evaluated the diagnosis of PBC in all individuals, and determined the zygosity of sets reported as identical by the analysis of 2 highly variable HLA class II regions and 5 short tandem repeats. Results: Eight of 16 sets of twins were monozygotic. In 5 of 8 monozygotic twin sets, both individuals had PBC (pairwise concordance rate, 0.63). Among the dizygotic twins (n = 8), no set was found to be concordant for PBC. Interestingly, the age at onset of disease was similar in 4 of 5 concordant sets of monozygotic pairs; however, there were differences in natural history and disease severity. Conclusions: The concordance rate of PBC in identical twins is among the highest reported in autoimmunity. However, discordant pairs were identified. The data show not only the role of genetics but also emphasize that either epigenetic factors and/or environment play a critical role.

Original languageEnglish (US)
Pages (from-to)485-492
Number of pages8
JournalGastroenterology
Volume127
Issue number2
DOIs
StatePublished - Aug 2004

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Keywords

  • AMA
  • CR
  • DZ
  • MZ
  • PBC
  • PCR
  • STR
  • antimitochondrial antibodies
  • concordance rate
  • dizygotic
  • monozygotic
  • polymerase chain reaction
  • primary biliary cirrhosis
  • short tandem repeat

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Selmi, C., Mayo, M. J., Bach, N., Ishibashi, H., Invernizzi, P., Gish, R. G., Gordon, S. C., Wright, H. I., Zweiban, B., Podda, M., & Gershwin, M. E. (2004). Primary biliary cirrhosis in monozygotic and dizygotic twins: Genetics, epigenetics, and environment. Gastroenterology, 127(2), 485-492. https://doi.org/10.1053/j.gastro.2004.05.005