Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism.
BACKGROUND and AIMS: Recent studies suggest that major histocompatibility complex-encoded susceptibility to primary sclerosing cholangitis (PSC) maps to the HLA B-TNFA region on chromosome 6p21.3. METHODS: The present study uses a standard polymerase chain reaction protocol to investigate the 16 com...
| প্রধান লেখক: | , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
2001
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| _version_ | 1826297809383456768 |
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| author | Norris, S Kondeatis, E Collins, R Satsangi, J Clare, M Chapman, R Stephens, H Harrison, P Vaughan, R Donaldson, P |
| author_facet | Norris, S Kondeatis, E Collins, R Satsangi, J Clare, M Chapman, R Stephens, H Harrison, P Vaughan, R Donaldson, P |
| author_sort | Norris, S |
| collection | OXFORD |
| description | BACKGROUND and AIMS: Recent studies suggest that major histocompatibility complex-encoded susceptibility to primary sclerosing cholangitis (PSC) maps to the HLA B-TNFA region on chromosome 6p21.3. METHODS: The present study uses a standard polymerase chain reaction protocol to investigate the 16 common alleles of the MICA locus as candidates in 2 patient populations (King's College Hospital, London, and John Radcliffe Hospital, Oxford). RESULTS: The MICA*002 allele was found in 4 of 62 (6.4%) patients and none of 50 patients vs. 41 of 118 (35%) controls (pc = 0.00018, odds ratio [OR] = 0.12, and P = 0.0000016, OR = 0.0, respectively). Overall, the MICA*008 allele was more common in PSC (gene frequency 66% vs. 48% of controls, P = 0.0023, OR = 2.11). However, unlike MICA*002 in which the difference was a result of the absence of MICA*002 heterozygotes, the MICA*008 association may be caused by an increased frequency of MICA*008 homozygosity in patients (58% vs. 22%, pc = 0.000015, OR = 5.01 and 58% vs. 22%, P = 0.0000056, OR = 4.51, respectively). Though MICA*008 is found on the ancestral 8.1 haplotype, stratification analysis indicates that this association is independent of B8 and other HLA haplotypes associated with PSC. CONCLUSIONS: The MICA*002 allele has a strong dominant effect in reducing the risk of PSC, whereas the increased risk of disease associated with MICA*008 may be a recessive effect requiring 2 copies of the MICA*008 allele. |
| first_indexed | 2024-03-07T04:37:18Z |
| format | Journal article |
| id | oxford-uuid:d067e6e7-018e-4f46-9d73-fcdfb316423f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:37:18Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:d067e6e7-018e-4f46-9d73-fcdfb316423f2022-03-27T07:49:37ZMapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d067e6e7-018e-4f46-9d73-fcdfb316423fEnglishSymplectic Elements at Oxford2001Norris, SKondeatis, ECollins, RSatsangi, JClare, MChapman, RStephens, HHarrison, PVaughan, RDonaldson, PBACKGROUND and AIMS: Recent studies suggest that major histocompatibility complex-encoded susceptibility to primary sclerosing cholangitis (PSC) maps to the HLA B-TNFA region on chromosome 6p21.3. METHODS: The present study uses a standard polymerase chain reaction protocol to investigate the 16 common alleles of the MICA locus as candidates in 2 patient populations (King's College Hospital, London, and John Radcliffe Hospital, Oxford). RESULTS: The MICA*002 allele was found in 4 of 62 (6.4%) patients and none of 50 patients vs. 41 of 118 (35%) controls (pc = 0.00018, odds ratio [OR] = 0.12, and P = 0.0000016, OR = 0.0, respectively). Overall, the MICA*008 allele was more common in PSC (gene frequency 66% vs. 48% of controls, P = 0.0023, OR = 2.11). However, unlike MICA*002 in which the difference was a result of the absence of MICA*002 heterozygotes, the MICA*008 association may be caused by an increased frequency of MICA*008 homozygosity in patients (58% vs. 22%, pc = 0.000015, OR = 5.01 and 58% vs. 22%, P = 0.0000056, OR = 4.51, respectively). Though MICA*008 is found on the ancestral 8.1 haplotype, stratification analysis indicates that this association is independent of B8 and other HLA haplotypes associated with PSC. CONCLUSIONS: The MICA*002 allele has a strong dominant effect in reducing the risk of PSC, whereas the increased risk of disease associated with MICA*008 may be a recessive effect requiring 2 copies of the MICA*008 allele. |
| spellingShingle | Norris, S Kondeatis, E Collins, R Satsangi, J Clare, M Chapman, R Stephens, H Harrison, P Vaughan, R Donaldson, P Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title | Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title_full | Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title_fullStr | Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title_full_unstemmed | Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title_short | Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism. |
| title_sort | mapping mhc encoded susceptibility and resistance in primary sclerosing cholangitis the role of mica polymorphism |
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