Haplotype sharing analysis identifies a retroviral dUTPase as candidate susceptibility gene for psoriasis.
The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to reside within a region around human leukocyte antigen-C spanning 250 kb, termed risk haplotype (RH) 1/2. By re-analyzing a published data set with a previously developed method, the haplotype sharing statistic, we confirm localization of PSORS1 to the RH1 region and refine its location to marker M6S168. We replicate this result in an independent patient sample. The target region harbors fragments of a human endogenous retrovirus K (HERV-K) endogenous retrovirus. Two single-nucleotide polymorphisms with alleles differing between high- and low-risk haplotypes are located within the HERV-K dUTPase. One of these encodes a predicted non-conserved Glu-Arg exchange. The HERV-K dUTPase is expressed in peripheral blood and in normal as well as lesional psoriatic skin. Our results indicate that an endogenous retroviral dUTPase constitutes a candidate gene for the PSORS1 mutation.
Foerster
John
J
Klinik für Dermatologie, Charité, Schumannstr., Berlin, Germany. john.foerster@charite.de
Nolte
Ilja
I
Junge
Judith
J
Bruinenberg
Marcel
M
Schweiger
Susann
S
Spaar
Katja
K
van der Steege
Gerrit
G
Ehlert
Claudia
C
Mulder
Marcel
M
Kalscheuer
Vera
V
Blumenthal-Barby
Elisa
E
Winter
Jennifer
J
Seeman
Petra
P
Ständer
Markward
M
Sterry
Wolfram
W
Te Meerman
Gerard
G
D002896:Chromosomes, Human, Pair 6; D020077:Endogenous Retroviruses / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*
D015236:HLA-C Antigens; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase