A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with a disease-associated susceptibility allele.
A susceptibility gene for psoriasis, a chronic skin disorder, resides in chromosome 6p near the HLA-C locus. Sequencing of the region has allowed the identification of a new gene, HCR. We found that HCR is highly polymorphic with at least 12 coding variants. An association study of the new HCR polymorphisms and the previously suggested susceptibility alleles HLA-Cw*0602 and corneodesmosin allele 5 (CD*5) with psoriasis revealed a specific HCR variant associated with psoriasis susceptibility. However, the HLA-Cw*0602 allele was rarer in controls and associated with a stronger relative risk. Association analysis did not support CD*5 as a psoriasis susceptibility allele in our sample of patients (n = 100) and population-matched controls (n = 93) from an isolated population. We found HCR to be overexpressed in keratinocytes of psoriatic lesions compared with paired samples of healthy skin. Our results suggest a potential role for HCR in the pathogenesis of psoriasis.
Asumalahti
K
K
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Laitinen
T
T
Itkonen-Vatjus
R
R
Lokki
M L
ML
Suomela
S
S
Snellman
E
E
Saarialho-Kere
U
U
Kere
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics; D015236:HLA-C Antigens / Q000096:biosynthesis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism
C412616:CCHCR1 protein, human; C109656:CDSN protein, human; D006023:Glycoproteins; D015236:HLA-C Antigens; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger