Abstract
Primary biliary cirrhosis (PBC) is a multifactorial autoimmune disease with inherited and environmental components in pathogenesis. It is exceptional among autoimmune diseases in showing strong heritability according to familial occurrence and monozygotic twins concordance, yet with weak associations with the usual genetic risk elements for autoimmunity, such as the HLA alleles. Among the latter, there is risk (at least in some populations) conferred by HLA DRB1*08 and possibly some protection by DRB1*11. However, the inconsistency among studies on HLA is surprising, given that PBC is a relatively homogenous disease entity. Among non-HLA genes, some studies implicate polymorphisms of genes for cytotoxic T-lymphocyte antigen-4, interleukin-2, or interleukin-10; polymorphisms of the vitamin D receptor could synergize with low sunlight exposure to create deficiency of the immunoregulatory factor, activated vitamin D. A new lead is available from the finding in female subjects with PBC of an increase in the degree of monosomy of the X chromosome that is presumed to carry immune response genes. A further suggested source of inquiry is the apparent protection of African-American women from PBC. Finally, data on inheritance should be sought in PBC by descent methodology, rather than by cross-sectional association studies in cases and control subjects, and based on analysis of a large number of families with an affected member through a worldwide effort.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 401-410 |
| Number of pages | 10 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 3 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2005 |
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ASJC Scopus subject areas
- Gastroenterology
Cite this
From bases to basis : Linking genetics to causation in primary biliary cirrhosis. / Invernizzi, Pietro; Selmi, Carlo; Mackay, Ian R.; Podda, Mauro; Gershwin, M. Eric.
In: Clinical Gastroenterology and Hepatology, Vol. 3, No. 5, 05.2005, p. 401-410.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - From bases to basis
T2 - Linking genetics to causation in primary biliary cirrhosis
AU - Invernizzi, Pietro
AU - Selmi, Carlo
AU - Mackay, Ian R.
AU - Podda, Mauro
AU - Gershwin, M. Eric
PY - 2005/5
Y1 - 2005/5
N2 - Primary biliary cirrhosis (PBC) is a multifactorial autoimmune disease with inherited and environmental components in pathogenesis. It is exceptional among autoimmune diseases in showing strong heritability according to familial occurrence and monozygotic twins concordance, yet with weak associations with the usual genetic risk elements for autoimmunity, such as the HLA alleles. Among the latter, there is risk (at least in some populations) conferred by HLA DRB1*08 and possibly some protection by DRB1*11. However, the inconsistency among studies on HLA is surprising, given that PBC is a relatively homogenous disease entity. Among non-HLA genes, some studies implicate polymorphisms of genes for cytotoxic T-lymphocyte antigen-4, interleukin-2, or interleukin-10; polymorphisms of the vitamin D receptor could synergize with low sunlight exposure to create deficiency of the immunoregulatory factor, activated vitamin D. A new lead is available from the finding in female subjects with PBC of an increase in the degree of monosomy of the X chromosome that is presumed to carry immune response genes. A further suggested source of inquiry is the apparent protection of African-American women from PBC. Finally, data on inheritance should be sought in PBC by descent methodology, rather than by cross-sectional association studies in cases and control subjects, and based on analysis of a large number of families with an affected member through a worldwide effort.
AB - Primary biliary cirrhosis (PBC) is a multifactorial autoimmune disease with inherited and environmental components in pathogenesis. It is exceptional among autoimmune diseases in showing strong heritability according to familial occurrence and monozygotic twins concordance, yet with weak associations with the usual genetic risk elements for autoimmunity, such as the HLA alleles. Among the latter, there is risk (at least in some populations) conferred by HLA DRB1*08 and possibly some protection by DRB1*11. However, the inconsistency among studies on HLA is surprising, given that PBC is a relatively homogenous disease entity. Among non-HLA genes, some studies implicate polymorphisms of genes for cytotoxic T-lymphocyte antigen-4, interleukin-2, or interleukin-10; polymorphisms of the vitamin D receptor could synergize with low sunlight exposure to create deficiency of the immunoregulatory factor, activated vitamin D. A new lead is available from the finding in female subjects with PBC of an increase in the degree of monosomy of the X chromosome that is presumed to carry immune response genes. A further suggested source of inquiry is the apparent protection of African-American women from PBC. Finally, data on inheritance should be sought in PBC by descent methodology, rather than by cross-sectional association studies in cases and control subjects, and based on analysis of a large number of families with an affected member through a worldwide effort.
UR - http://www.scopus.com/inward/record.url?scp=18144383173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18144383173&partnerID=8YFLogxK
U2 - 10.1016/S1542-3565(04)00678-0
DO - 10.1016/S1542-3565(04)00678-0
M3 - Article
C2 - 15880308
AN - SCOPUS:18144383173
VL - 3
SP - 401
EP - 410
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 5
ER -