Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: The role of MICA polymorphism

99Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.
Get full text

Abstract

Background & 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.

Cite

CITATION STYLE

APA

Norris, S., Kondeatis, E., Collins, R., Satsangi, J., Clare, M., Chapman, R., … Donaldson, P. (2001). Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: The role of MICA polymorphism. Gastroenterology, 120(6), 1475–1482. https://doi.org/10.1053/gast.2001.24041

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free