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

被引:364
作者
Selmi, C
Mayo, MJ
Bach, N
Ishibashi, H
Invernizzi, P
Gish, RG
Gordon, SC
Wright, HI
Zweiban, B
Podda, M
Gershwin, ME
机构
[1] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA
[2] Univ Milan, Div Internal Med, Dept Med Surg & Dent, Milan, Italy
[3] Univ Texas SW, Dept Internal Med, Dallas, TX USA
[4] Mt Sinai Univ, Dept Liver Dis, New York, NY USA
[5] Natl Nagasaki Med Ctr, Clin Res Ctr, Nagasaki, Japan
[6] Sutter Calif Pacific Med Ctr, Dept Transplant, San Francisco, CA USA
[7] William Beaumont Hosp, Div Gastroenterol & Hepatol, Royal Oak, MI USA
[8] Nazih Zuhdi Transplant Inst, Oklahoma City, OK USA
[9] So Calif Kaiser Permanente Hosp, Div Gastroenterol, Panorama City, CA USA
关键词
D O I
10.1053/j.gastro.2004.05.005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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页码:485 / 492
页数:8
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