The University of Southampton
University of Southampton Institutional Repository

Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus
PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.
589-597
Asumalahti, Kati
25c7ca2c-d39e-491f-bc85-31a09fb9ed9e
Veal, Colin
197cf852-a35a-426a-af63-1c2c936eb704
Laitinen, Tarja
b1182047-4f8f-4d6b-8d90-b6cf13009f5a
Suomela, Sari
d3fca8a3-a903-46ed-a63f-b8c533498c6c
Allen, Michael
a177adf5-62e3-4e62-b154-d9bf4d0cae5a
Elomaa, Outi
01fd16a2-aeb5-48b2-8456-50ccbfbd887a
Moser, Michael
92a14b9a-5801-4e40-bfa0-a9a5b922f7c7
De Cid, Rafael
6ab84216-db6f-4b49-ae1c-28d3c3083c58
Ripatti, Samuli
705fa391-c779-4941-814c-8ce1f8fbefb7
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Marcusson, Jan A.
982a7806-4af5-4b6c-9400-6b926eb727b0
Nakagawa, Hidemi
4cfb02f5-81ad-4d87-a8e6-154c84580d1f
Lazaro, Conxi
34576bd1-4cfb-4b16-9a51-78bdd7057bd7
Estivill, Xavier
adc70527-72da-45ac-a5c1-ccc0af8cee19
Capon, Francesca
fb317075-e078-40eb-9349-a227a657cad8
Novelli, Giuseppe
85ec18ca-64c0-400a-8ded-88dc4c0fe7c9
Saarialho-Kere, Ulpu
d3a10378-4e3e-45ee-86c4-c9ba28dd1522
Barker, Jonathan
a2d664e4-6875-4017-8cfe-500c2709a34e
Trembath, Richard
0b430b7a-58b8-4ad0-8cd0-1fed864c8add
Kere, Juha
57c301de-f111-4552-a585-13eed945bdfc
Asumalahti, Kati
25c7ca2c-d39e-491f-bc85-31a09fb9ed9e
Veal, Colin
197cf852-a35a-426a-af63-1c2c936eb704
Laitinen, Tarja
b1182047-4f8f-4d6b-8d90-b6cf13009f5a
Suomela, Sari
d3fca8a3-a903-46ed-a63f-b8c533498c6c
Allen, Michael
a177adf5-62e3-4e62-b154-d9bf4d0cae5a
Elomaa, Outi
01fd16a2-aeb5-48b2-8456-50ccbfbd887a
Moser, Michael
92a14b9a-5801-4e40-bfa0-a9a5b922f7c7
De Cid, Rafael
6ab84216-db6f-4b49-ae1c-28d3c3083c58
Ripatti, Samuli
705fa391-c779-4941-814c-8ce1f8fbefb7
Vorechovsky, Igor
7245de2f-8c9b-4034-8935-9a451d9b682e
Marcusson, Jan A.
982a7806-4af5-4b6c-9400-6b926eb727b0
Nakagawa, Hidemi
4cfb02f5-81ad-4d87-a8e6-154c84580d1f
Lazaro, Conxi
34576bd1-4cfb-4b16-9a51-78bdd7057bd7
Estivill, Xavier
adc70527-72da-45ac-a5c1-ccc0af8cee19
Capon, Francesca
fb317075-e078-40eb-9349-a227a657cad8
Novelli, Giuseppe
85ec18ca-64c0-400a-8ded-88dc4c0fe7c9
Saarialho-Kere, Ulpu
d3a10378-4e3e-45ee-86c4-c9ba28dd1522
Barker, Jonathan
a2d664e4-6875-4017-8cfe-500c2709a34e
Trembath, Richard
0b430b7a-58b8-4ad0-8cd0-1fed864c8add
Kere, Juha
57c301de-f111-4552-a585-13eed945bdfc

Asumalahti, Kati, Veal, Colin, Laitinen, Tarja, Suomela, Sari, Allen, Michael, Elomaa, Outi, Moser, Michael, De Cid, Rafael, Ripatti, Samuli, Vorechovsky, Igor, Marcusson, Jan A., Nakagawa, Hidemi, Lazaro, Conxi, Estivill, Xavier, Capon, Francesca, Novelli, Giuseppe, Saarialho-Kere, Ulpu, Barker, Jonathan, Trembath, Richard and Kere, Juha (2002) Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus. Human Molecular Genetics, 11 (5), 589-597. (doi:10.1093/hmg/11.5.589).

Record type: Article

Abstract

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.

Full text not available from this repository.

More information

Published date: 2002

Identifiers

Local EPrints ID: 24615
URI: http://eprints.soton.ac.uk/id/eprint/24615
PURE UUID: f74411ca-8ede-4cc0-a637-bced6c560124

Catalogue record

Date deposited: 03 Apr 2006
Last modified: 15 Jul 2019 19:17

Export record

Altmetrics

Contributors

Author: Kati Asumalahti
Author: Colin Veal
Author: Tarja Laitinen
Author: Sari Suomela
Author: Michael Allen
Author: Outi Elomaa
Author: Michael Moser
Author: Rafael De Cid
Author: Samuli Ripatti
Author: Jan A. Marcusson
Author: Hidemi Nakagawa
Author: Conxi Lazaro
Author: Xavier Estivill
Author: Francesca Capon
Author: Giuseppe Novelli
Author: Ulpu Saarialho-Kere
Author: Jonathan Barker
Author: Richard Trembath
Author: Juha Kere

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×