Severe Hepatic Fibrosis in Schistosoma mansoni Infection Is Controlled by a Major Locus That Is Closely Linked to the Interferon-γ Receptor Gene
Lethal disease due to hepatic periportal fibrosis occurs in 2%–10% of subjects infected by Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development. Schistosoma mansoni...
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| Veröffentlicht in: | American journal of human genetics 1999-09, Vol.65 (3), p.709-721 |
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| creator | Dessein, Alain J. Hillaire, Dominique Elwali, Nasr Eldin M.A. Marquet, Sandrine Mohamed-Ali, Qurashi Mirghani, Adil Henri, Sandrine Abdelhameed, Ahmed A. Saeed, Osman K. Magzoub, Mubarak M.A. Abel, Laurent |
| description | Lethal disease due to hepatic periportal fibrosis occurs in 2%–10% of subjects infected by
Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development.
Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with .16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains |
| doi_str_mv | 10.1086/302526 |
| format | Article |
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Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development.
Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with .16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the
IFN-γR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-γ. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the
IFN-γR1 gene could determine severe hepatic disease due to
S. mansoni infection and that the
IFN-γR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1086/302526</identifier><identifier>PMID: 10441577</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Chicago, IL: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Child ; Chromosomes, Human, Pair 6 - genetics ; Diseases caused by trematodes ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Helminthic diseases ; Hepatic fibrosis ; Humans ; Infectious diseases ; Interferon gamma Receptor ; Interferon-γ ; Life Sciences ; Liver Cirrhosis - diagnostic imaging ; Liver Cirrhosis - genetics ; Liver Cirrhosis - parasitology ; Liver Diseases, Parasitic - complications ; Liver Diseases, Parasitic - genetics ; Liver Diseases, Parasitic - parasitology ; Lod Score ; Male ; Medical sciences ; Middle Aged ; Odds Ratio ; Parasitic diseases ; Pedigree ; Penetrance ; Portal hypertension ; Receptors, Interferon - genetics ; Schistosomiases ; Schistosomiasis ; Schistosomiasis mansoni - complications ; Schistosomiasis mansoni - genetics ; Schistosomiasis mansoni - parasitology ; Sex Factors ; Sudan ; Time Factors ; Tropical medicine ; Ultrasonography</subject><ispartof>American journal of human genetics, 1999-09, Vol.65 (3), p.709-721</ispartof><rights>1999 The American Society of Human Genetics</rights><rights>1999 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-6db9c185b3a0f827222b987ba662380d4091621d0ac350d787e31a5f4747e0ff3</citedby><cites>FETCH-LOGICAL-c466t-6db9c185b3a0f827222b987ba662380d4091621d0ac350d787e31a5f4747e0ff3</cites><orcidid>0000-0001-7011-6496</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377977/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002929707623222$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1973371$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10441577$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://amu.hal.science/hal-01595986$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Dessein, Alain J.</creatorcontrib><creatorcontrib>Hillaire, Dominique</creatorcontrib><creatorcontrib>Elwali, Nasr Eldin M.A.</creatorcontrib><creatorcontrib>Marquet, Sandrine</creatorcontrib><creatorcontrib>Mohamed-Ali, Qurashi</creatorcontrib><creatorcontrib>Mirghani, Adil</creatorcontrib><creatorcontrib>Henri, Sandrine</creatorcontrib><creatorcontrib>Abdelhameed, Ahmed A.</creatorcontrib><creatorcontrib>Saeed, Osman K.</creatorcontrib><creatorcontrib>Magzoub, Mubarak M.A.</creatorcontrib><creatorcontrib>Abel, Laurent</creatorcontrib><title>Severe Hepatic Fibrosis in Schistosoma mansoni Infection Is Controlled by a Major Locus That Is Closely Linked to the Interferon-γ Receptor Gene</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Lethal disease due to hepatic periportal fibrosis occurs in 2%–10% of subjects infected by
Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development.
Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with .16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the
IFN-γR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-γ. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the
IFN-γR1 gene could determine severe hepatic disease due to
S. mansoni infection and that the
IFN-γR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Chromosomes, Human, Pair 6 - genetics</subject><subject>Diseases caused by trematodes</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Genetic Predisposition to Disease</subject><subject>Helminthic diseases</subject><subject>Hepatic fibrosis</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Interferon gamma Receptor</subject><subject>Interferon-γ</subject><subject>Life Sciences</subject><subject>Liver Cirrhosis - diagnostic imaging</subject><subject>Liver Cirrhosis - genetics</subject><subject>Liver Cirrhosis - parasitology</subject><subject>Liver Diseases, Parasitic - complications</subject><subject>Liver Diseases, Parasitic - genetics</subject><subject>Liver Diseases, Parasitic - parasitology</subject><subject>Lod Score</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Parasitic diseases</subject><subject>Pedigree</subject><subject>Penetrance</subject><subject>Portal hypertension</subject><subject>Receptors, Interferon - genetics</subject><subject>Schistosomiases</subject><subject>Schistosomiasis</subject><subject>Schistosomiasis mansoni - complications</subject><subject>Schistosomiasis mansoni - genetics</subject><subject>Schistosomiasis mansoni - parasitology</subject><subject>Sex Factors</subject><subject>Sudan</subject><subject>Time Factors</subject><subject>Tropical medicine</subject><subject>Ultrasonography</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkdFu0zAUhiMEYmXAIyBfoElcBOw4seMbpKlia6UgJDauLcc5IR6JXWy3Uh-DZ-E9eKa5SwVlV5bs7_y_7S_LXhP8nuCafaC4qAr2JFuQivKcMVw9zRYY4yIXheBn2YsQ7jAmpMb0eXZGcFmSivNF9usGduABrWCjotHoyrTeBROQsehGDyZEF9yk0KRscNagte1BR-MsWge0dDZ6N47QoXaPFPqs7pxHjdPbgG4HFR-Y0QUY96gx9kfiokNxgBQTwffgnc3__EZfQcMmptFrsPAye9arMcCr43qefbv6dLtc5c2X6_Xyssl1yVjMWdcKTeqqpQr3dcGLomhFzVvFWEFr3JVYEFaQDitNK9zxmgMlqupLXnLAfU_Ps49z7mbbTtBpSG9Ro9x4Mym_l04Z-f-JNYP87naSUM4F5yng3RwwPBpbXTbysIdJJSpRsx1J7MWxzLufWwhRTiZoGEdlwW2DZEIwWpUnoE4agof-bzLB8mBazqYT-Ob0-ifYrDYBb4-AClqNvVdWm_CPE5xSfijEMwbpr3cGvAzagNXQGZ9My86Zx9X3B47A1Q</recordid><startdate>19990901</startdate><enddate>19990901</enddate><creator>Dessein, Alain J.</creator><creator>Hillaire, Dominique</creator><creator>Elwali, Nasr Eldin M.A.</creator><creator>Marquet, Sandrine</creator><creator>Mohamed-Ali, Qurashi</creator><creator>Mirghani, Adil</creator><creator>Henri, Sandrine</creator><creator>Abdelhameed, Ahmed A.</creator><creator>Saeed, Osman K.</creator><creator>Magzoub, Mubarak M.A.</creator><creator>Abel, Laurent</creator><general>Elsevier Inc</general><general>University of Chicago Press</general><general>Elsevier (Cell Press)</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7011-6496</orcidid></search><sort><creationdate>19990901</creationdate><title>Severe Hepatic Fibrosis in Schistosoma mansoni Infection Is Controlled by a Major Locus That Is Closely Linked to the Interferon-γ Receptor Gene</title><author>Dessein, Alain J. ; Hillaire, Dominique ; Elwali, Nasr Eldin M.A. ; Marquet, Sandrine ; Mohamed-Ali, Qurashi ; Mirghani, Adil ; Henri, Sandrine ; Abdelhameed, Ahmed A. ; Saeed, Osman K. ; Magzoub, Mubarak M.A. ; Abel, Laurent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-6db9c185b3a0f827222b987ba662380d4091621d0ac350d787e31a5f4747e0ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Chromosomes, Human, Pair 6 - genetics</topic><topic>Diseases caused by trematodes</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Genetic Predisposition to Disease</topic><topic>Helminthic diseases</topic><topic>Hepatic fibrosis</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Interferon gamma Receptor</topic><topic>Interferon-γ</topic><topic>Life Sciences</topic><topic>Liver Cirrhosis - diagnostic imaging</topic><topic>Liver Cirrhosis - genetics</topic><topic>Liver Cirrhosis - parasitology</topic><topic>Liver Diseases, Parasitic - complications</topic><topic>Liver Diseases, Parasitic - genetics</topic><topic>Liver Diseases, Parasitic - parasitology</topic><topic>Lod Score</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Odds Ratio</topic><topic>Parasitic diseases</topic><topic>Pedigree</topic><topic>Penetrance</topic><topic>Portal hypertension</topic><topic>Receptors, Interferon - genetics</topic><topic>Schistosomiases</topic><topic>Schistosomiasis</topic><topic>Schistosomiasis mansoni - complications</topic><topic>Schistosomiasis mansoni - genetics</topic><topic>Schistosomiasis mansoni - parasitology</topic><topic>Sex Factors</topic><topic>Sudan</topic><topic>Time Factors</topic><topic>Tropical medicine</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dessein, Alain J.</creatorcontrib><creatorcontrib>Hillaire, Dominique</creatorcontrib><creatorcontrib>Elwali, Nasr Eldin M.A.</creatorcontrib><creatorcontrib>Marquet, Sandrine</creatorcontrib><creatorcontrib>Mohamed-Ali, Qurashi</creatorcontrib><creatorcontrib>Mirghani, Adil</creatorcontrib><creatorcontrib>Henri, Sandrine</creatorcontrib><creatorcontrib>Abdelhameed, Ahmed A.</creatorcontrib><creatorcontrib>Saeed, Osman K.</creatorcontrib><creatorcontrib>Magzoub, Mubarak M.A.</creatorcontrib><creatorcontrib>Abel, Laurent</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dessein, Alain J.</au><au>Hillaire, Dominique</au><au>Elwali, Nasr Eldin M.A.</au><au>Marquet, Sandrine</au><au>Mohamed-Ali, Qurashi</au><au>Mirghani, Adil</au><au>Henri, Sandrine</au><au>Abdelhameed, Ahmed A.</au><au>Saeed, Osman K.</au><au>Magzoub, Mubarak M.A.</au><au>Abel, Laurent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Severe Hepatic Fibrosis in Schistosoma mansoni Infection Is Controlled by a Major Locus That Is Closely Linked to the Interferon-γ Receptor Gene</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>1999-09-01</date><risdate>1999</risdate><volume>65</volume><issue>3</issue><spage>709</spage><epage>721</epage><pages>709-721</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><coden>AJHGAG</coden><abstract>Lethal disease due to hepatic periportal fibrosis occurs in 2%–10% of subjects infected by
Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development.
Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with .16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the
IFN-γR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-γ. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the
IFN-γR1 gene could determine severe hepatic disease due to
S. mansoni infection and that the
IFN-γR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.</abstract><cop>Chicago, IL</cop><pub>Elsevier Inc</pub><pmid>10441577</pmid><doi>10.1086/302526</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7011-6496</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of human genetics, 1999-09, Vol.65 (3), p.709-721 |
| issn | 0002-9297 1537-6605 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1377977 |
| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult Biological and medical sciences Child Chromosomes, Human, Pair 6 - genetics Diseases caused by trematodes Female Genetic Markers Genetic Predisposition to Disease Helminthic diseases Hepatic fibrosis Humans Infectious diseases Interferon gamma Receptor Interferon-γ Life Sciences Liver Cirrhosis - diagnostic imaging Liver Cirrhosis - genetics Liver Cirrhosis - parasitology Liver Diseases, Parasitic - complications Liver Diseases, Parasitic - genetics Liver Diseases, Parasitic - parasitology Lod Score Male Medical sciences Middle Aged Odds Ratio Parasitic diseases Pedigree Penetrance Portal hypertension Receptors, Interferon - genetics Schistosomiases Schistosomiasis Schistosomiasis mansoni - complications Schistosomiasis mansoni - genetics Schistosomiasis mansoni - parasitology Sex Factors Sudan Time Factors Tropical medicine Ultrasonography |
| title | Severe Hepatic Fibrosis in Schistosoma mansoni Infection Is Controlled by a Major Locus That Is Closely Linked to the Interferon-γ Receptor Gene |
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