Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients.
Artikel i vetenskaplig tidskrift, 2000

Psoriasis vulgaris is strongly associated with certain human leukocyte antigens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was utilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haplotype information were sequenced. The results confirmed the identity of the Cw6 allele in affected individuals with the consensus sequence for Cw*0602. We screened the set of families for psoriasis patients homozygous for Cw6 and found 11 individuals with a mean age at onset of 16.1 years. The corresponding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-negatives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t167/nt45). This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested candidate gene in the region. The maximum nonparametric linkage (NPL) value was also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the highest degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a polygenic theory.

Humans

Family Health

Microsatellite Repeats

Sweden

Sequence Analysis

Genotype

Polymorphism

DNA

chemistry

Genetic

HLA-C Antigens

genetics

pathology

Female

Pedigree

Psoriasis

Alleles

genetics

Male

genetics

DNA

Glycoproteins

Lod Score

genetics

Haplotypes

Författare

Charlotta Enerbäck

Göteborgs universitet

Staffan Nilsson

Institutionen för matematik, Matematisk statistik

Göteborgs universitet

Fredrik Enlund

Göteborgs universitet

Annica Inerot

Göteborgs universitet

Lena Samuelsson

Göteborgs universitet

Jan Wahlström

Göteborgs universitet

Gunnar Swanbeck

Göteborgs universitet

Tommy Martinsson

Göteborgs universitet

Archives of Dermatological Research

0340-3696 (ISSN)

Vol. 292 11 525-30

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1007/s004030000175

PubMed

11194889