A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes
Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fcγ-RIIa and IL1-R...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2013-12-01
|
| Series: | Kidney & Blood Pressure Research |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/355744 |
| _version_ | 1818204896563822592 |
|---|---|
| author | Ulf Persson Birgitta Gullstrand Åsa Pettersson Gunnar Sturfelt Lennart Truedsson Mårten Segelmark |
| author_facet | Ulf Persson Birgitta Gullstrand Åsa Pettersson Gunnar Sturfelt Lennart Truedsson Mårten Segelmark |
| author_sort | Ulf Persson |
| collection | DOAJ |
| description | Background/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fcγ-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegener's granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fcγ-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases. |
| first_indexed | 2024-12-12T03:48:31Z |
| format | Article |
| id | doaj.art-f802b0ab02734aec81e0c4f6547c4f90 |
| institution | Directory Open Access Journal |
| issn | 1420-4096 1423-0143 |
| language | English |
| last_indexed | 2024-12-12T03:48:31Z |
| publishDate | 2013-12-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney & Blood Pressure Research |
| spelling | doaj.art-f802b0ab02734aec81e0c4f6547c4f902022-12-22T00:39:28ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432013-12-0137664164810.1159/000355744355744A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa GenesUlf PerssonBirgitta GullstrandÅsa PetterssonGunnar SturfeltLennart TruedssonMårten SegelmarkBackground/Aims: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fcγ-RIIa and IL1-Ra. Patients and Methods: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegener's granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. Results: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fcγ-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. Conclusion: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.http://www.karger.com/Article/FullText/355744ANCAGeneticsGranulomatosis with polyangiitisMicroscopic polyangiitisWegener’s granulomatosis |
| spellingShingle | Ulf Persson Birgitta Gullstrand Åsa Pettersson Gunnar Sturfelt Lennart Truedsson Mårten Segelmark A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes Kidney & Blood Pressure Research ANCA Genetics Granulomatosis with polyangiitis Microscopic polyangiitis Wegener’s granulomatosis |
| title | A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes |
| title_full | A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes |
| title_fullStr | A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes |
| title_full_unstemmed | A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes |
| title_short | A Candidate Gene Approach to ANCA-Associated Vasculitis Reveals Links to the C3 and CTLA-4 Genes but not to the IL1-Ra And Fcγ-RIIa Genes |
| title_sort | candidate gene approach to anca associated vasculitis reveals links to the c3 and ctla 4 genes but not to the il1 ra and fc 947 riia genes |
| topic | ANCA Genetics Granulomatosis with polyangiitis Microscopic polyangiitis Wegener’s granulomatosis |
| url | http://www.karger.com/Article/FullText/355744 |
| work_keys_str_mv | AT ulfpersson acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT birgittagullstrand acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT asapettersson acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT gunnarsturfelt acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT lennarttruedsson acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT martensegelmark acandidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT ulfpersson candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT birgittagullstrand candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT asapettersson candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT gunnarsturfelt candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT lennarttruedsson candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes AT martensegelmark candidategeneapproachtoancaassociatedvasculitisrevealslinkstothec3andctla4genesbutnottotheil1raandfc947riiagenes |