Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients.
Journal article, 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
Author
Charlotta Enerbäck
University of Gothenburg
Staffan Nilsson
Department of Mathematics, Mathematical Statistics
University of Gothenburg
Fredrik Enlund
University of Gothenburg
Annica Inerot
University of Gothenburg
Lena Samuelsson
University of Gothenburg
Jan Wahlström
University of Gothenburg
Gunnar Swanbeck
University of Gothenburg
Tommy Martinsson
University of Gothenburg
Archives of Dermatological Research
0340-3696 (ISSN)
Vol. 292 11 525-30Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1007/s004030000175
PubMed
11194889