Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment.
OBJECTIVE
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.
Selmi
Carlo
C
Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, 95616, USA.
Mayo
Marlyn J
MJ
Bach
Nancy
N
Ishibashi
Hiromi
H
Invernizzi
Pietro
P
Gish
Robert G
RG
Gordon
Stuart C
SC
Wright
Harlan I
HI
Zweiban
Bruce
B
Podda
Mauro
M
Gershwin
M Eric
ME
D000328:Adult; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic