A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis.
<h4>Background aims</h4>Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the PNPLA3 gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the dis...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9102ced40ef94cce837eefe5c840c95d |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9102ced40ef94cce837eefe5c840c95d |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9102ced40ef94cce837eefe5c840c95d2021-11-18T07:54:18ZA frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis.1932-620310.1371/journal.pone.0058734https://doaj.org/article/9102ced40ef94cce837eefe5c840c95d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23505555/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background aims</h4>Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the PNPLA3 gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the disease course of PSC.<h4>Methods</h4>The I148M polymorphism was genotyped in 121 German PSC patients of a long-term prospective cohort and 347 Norwegian PSC patients.<h4>Results</h4>In the prospective German cohort, actuarial survival free of liver transplantation was significantly reduced for I148M carriers (p = 0.011) compared to wildtype patients. This effect was restricted to patients with severe disease, as defined by development of dominant stenosis (DS) requiring endoscopic intervention. DS patients showed markedly decreased survival (p = 0.004) when carrying the I148M variant (I148M: mean 13.8 years; 95% confidence interval: 11.6-16.0 vs. wildtype: mean 18.6 years; 95% confidence interval: 16.3-20.9) while there was no impact on survival in patients without a DS (p = 0.87). In line with previous observations of sex specific effects of the I148M polymorphism, the effect on survival was further restricted to male patients (mean survival 11.9 years; 95% confidence interval: 10.0-14.0 in I148M carriers vs. 18.8 years; 95% confidence interval: 16.2-21.5 in wildtype; p<0.001) while female patients were unaffected by the polymorphism (p = 0.65). These sex specific findings were validated in the Norwegian cohort (p = 0.013).<h4>Conclusions</h4>In male PSC patients with severe disease with bile duct stenosis requiring intervention, the common I148M variant of the PNPLA3 gene is a risk factor for reduced survival.Kilian FriedrichChristian RuppJohannes Roksund HovNiels SteinebrunnerKarl-Heinz WeissAdolf StiehlMaik BrunePetra Kloeters Yvonne SchaeferPeter SchemmerPeter SauerPeter SchirmacherHeiko RunzTom Hemming KarlsenWolfgang StremmelDaniel Nils GotthardtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58734 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Kilian Friedrich Christian Rupp Johannes Roksund Hov Niels Steinebrunner Karl-Heinz Weiss Adolf Stiehl Maik Brune Petra Kloeters Yvonne Schaefer Peter Schemmer Peter Sauer Peter Schirmacher Heiko Runz Tom Hemming Karlsen Wolfgang Stremmel Daniel Nils Gotthardt A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| description |
<h4>Background aims</h4>Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the PNPLA3 gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the disease course of PSC.<h4>Methods</h4>The I148M polymorphism was genotyped in 121 German PSC patients of a long-term prospective cohort and 347 Norwegian PSC patients.<h4>Results</h4>In the prospective German cohort, actuarial survival free of liver transplantation was significantly reduced for I148M carriers (p = 0.011) compared to wildtype patients. This effect was restricted to patients with severe disease, as defined by development of dominant stenosis (DS) requiring endoscopic intervention. DS patients showed markedly decreased survival (p = 0.004) when carrying the I148M variant (I148M: mean 13.8 years; 95% confidence interval: 11.6-16.0 vs. wildtype: mean 18.6 years; 95% confidence interval: 16.3-20.9) while there was no impact on survival in patients without a DS (p = 0.87). In line with previous observations of sex specific effects of the I148M polymorphism, the effect on survival was further restricted to male patients (mean survival 11.9 years; 95% confidence interval: 10.0-14.0 in I148M carriers vs. 18.8 years; 95% confidence interval: 16.2-21.5 in wildtype; p<0.001) while female patients were unaffected by the polymorphism (p = 0.65). These sex specific findings were validated in the Norwegian cohort (p = 0.013).<h4>Conclusions</h4>In male PSC patients with severe disease with bile duct stenosis requiring intervention, the common I148M variant of the PNPLA3 gene is a risk factor for reduced survival. |
| format |
article |
| author |
Kilian Friedrich Christian Rupp Johannes Roksund Hov Niels Steinebrunner Karl-Heinz Weiss Adolf Stiehl Maik Brune Petra Kloeters Yvonne Schaefer Peter Schemmer Peter Sauer Peter Schirmacher Heiko Runz Tom Hemming Karlsen Wolfgang Stremmel Daniel Nils Gotthardt |
| author_facet |
Kilian Friedrich Christian Rupp Johannes Roksund Hov Niels Steinebrunner Karl-Heinz Weiss Adolf Stiehl Maik Brune Petra Kloeters Yvonne Schaefer Peter Schemmer Peter Sauer Peter Schirmacher Heiko Runz Tom Hemming Karlsen Wolfgang Stremmel Daniel Nils Gotthardt |
| author_sort |
Kilian Friedrich |
| title |
A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| title_short |
A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| title_full |
A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| title_fullStr |
A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| title_full_unstemmed |
A frequent PNPLA3 variant is a sex specific disease modifier in PSC patients with bile duct stenosis. |
| title_sort |
frequent pnpla3 variant is a sex specific disease modifier in psc patients with bile duct stenosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9102ced40ef94cce837eefe5c840c95d |
| work_keys_str_mv |
AT kilianfriedrich afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT christianrupp afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT johannesroksundhov afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT nielssteinebrunner afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT karlheinzweiss afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT adolfstiehl afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT maikbrune afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT petrakloetersyvonneschaefer afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT peterschemmer afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT petersauer afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT peterschirmacher afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT heikorunz afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT tomhemmingkarlsen afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT wolfgangstremmel afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT danielnilsgotthardt afrequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT kilianfriedrich frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT christianrupp frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT johannesroksundhov frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT nielssteinebrunner frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT karlheinzweiss frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT adolfstiehl frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT maikbrune frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT petrakloetersyvonneschaefer frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT peterschemmer frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT petersauer frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT peterschirmacher frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT heikorunz frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT tomhemmingkarlsen frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT wolfgangstremmel frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis AT danielnilsgotthardt frequentpnpla3variantisasexspecificdiseasemodifierinpscpatientswithbileductstenosis |
| _version_ |
1718422789710413824 |