Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment.
نویسندگان
چکیده
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.
منابع مشابه
Primary Biliary Cirrhosis: Family Stories
Primary biliary cirrhosis (PBC) is a chronic immune-mediated cholestatic liver disease of unknown aetiology which affects mostly women in middle age. Familial PBC is when PBC affects more than one member of the same family, and data suggest that first-degree relatives of PBC patients have an increased risk of developing the disease. Most often, these familial clusters involve mother-daughter pa...
متن کاملBiliary lipid composition in monozygotic and dizygotic pairs of twins.
The relative contribution of genetic factors to biliary and serum lipid composition was studied in 17 monozygotic and 18 dizygotic middle aged male pairs of twins. Cholesterol precursors, squalene and Methylated sterols which reflect the activity of cholesterol synthesis were also measured. Pairwise intraclass correlations were determined for monozygotic and dizygotic twin pairs and heritabilit...
متن کامل11th Medinterna International Meeting: what did we learn?
development of autoimmune diseases were demonstrated by the example of primary biliary cirrhosis. The already known increased risk in first-degree relatives of PBC2 patients and the high concordance in monozygotic compared to dizygotic twins associated with bacteria, viruses, xenobiotics or chemical compounds (e.g., drugs like acetaminophen) have the potential to modify host proteins to render ...
متن کاملEpigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is an autoimmune chronic cholestatic liver disease with a strong genetic susceptibility due to the high concordance in monozygotic (MZ) twins and a striking female predominance. Women with PBC manifest an enhanced X monosomy rate in peripheral lymphocytes and we thus hypothesized an X chromosome epigenetic component to explain PBC female prevalence. While most ge...
متن کاملHeritability of testis size.
Testis size is an important feature of male pubertal development. The genetic and environmental contributions to variation in human testis size have hardly been studied. We estimated the heritability of human testicular size in a group of mono- and dizygotic twins and their non-twin brothers (145 twins and 20 brothers from 95 families). Participants were 18 years old on average and all had reac...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Gastroenterology
دوره 127 2 شماره
صفحات -
تاریخ انتشار 2004