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- Alenius, Gerd-Marie, et al.
(författare)
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Analysis of 6 genetic loci for disease susceptibility in psoriatic arthritis.
- 2004
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Ingår i: The Journal of rheumatology. - 0315-162X .- 1499-2752. ; 31:11, s. 2230-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the association of several autoimmune disease susceptibility loci in a population of patients with psoriasis and defined joint disease from northern Sweden. METHOD: One hundred twenty patients with psoriasis and defined joint disease were examined clinically, radiologically, and with laboratory-based analyses. Disease classification was based on peripheral and/or axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21 (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38 microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four controls with the same ethnic background as the patients were randomly selected from the same region of Sweden. RESULTS: An association was found with one of the markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus showed nominal p values of < 0.05. After applying the Bonferroni correction for multiple analyses these markers did not reach significance. No other marker showed significant association. In a subgroup of the patients, possible linkage disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and B62 was analyzed. A significant linkage (p = 0.0001) was found. CONCLUSION: We identified an association between psoriatic arthritis and one of the microsatellite markers within the TNFB locus at the HLA region on chromosome 6. Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found.
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| 2. |
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| 3. |
- Friberg, Camilla, 1976
(författare)
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Genetic Studies of Psoriasis and Psoriatic Arthritis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis and psoriatic arthritis are common chronic immune-mediated diseases of the skin and joints. Psoriasis affects approximately 2-3 % of the Caucasian population and about 30 % of all psoriasis patients develop psoriatic arthritis. Both diseases have a strong genetic component but are also affected by environmental factors and are thus regarded as multifactorial. A major genetic factor contributing to susceptibility to both diseases is believed to reside at the HLA locus on chromosome 6, although different alleles within this locus have been found to associate with the respective diseases. While this is the strongest and most replicated locus, other susceptibility loci have also been identified through genome-wide linkage studies and candidate gene approaches. The studies in this thesis aimed at refining two susceptibility loci for psoriasis identified with linkage analysis, 3q21 and 5q31-32, with a special emphasis on the PSORS5 region on chromosome 3q21. Another purpose was to investigate whether several autoimmune-associating genes and genomic regions are susceptibility factors for psoriasis/psoriatic arthritis. Association studies on a psoriatic arthritis case-control material revealed an association with a marker in the TNFB locus within the HLA region. Linkage disequilibrium (LD) between TNFB123 and certain HLA-B antigens was also found. Due to the strong LD within this region, it is difficult to identify the disease-causing allele. No association was found with a microsatellite marker within the CTLA-4 gene, previously associated with rheumatoid arthritis (RA), nor with the eight genotyped markers within the PSORS5 region. This region was identified in a data set of southwestern Swedish families with psoriasis and arthritic symptoms. The lack of association is consonant with the hypothesis of a founder mutation in this region. The 5q31-32 region was refined with 34 markers in multi-affected psoriasis families. We obtained a peak non-parametric linkage value of 3.1 for marker D5S436 in a subgroup of patients with arthritic symptoms. However, no association was found with 3 SNPs reported to associate with RA and Crohn?s disease (CD) and to change the functional activity of 2 cation transporters, SLC22A4 and SLC22A5. These results support the existence of a susceptibility region for psoriasis on chromosome 5q32, probably involved in the arthritic phenotype and not caused by the 3 SNPs within SLC22A4 and SLC22A5. Analysis of two candidate genes, CSTA and ZNF148, within the linkage region of PSORS5 yielded no significant association. It is therefore unlikely that they harbor the genetic cause of psoriasis at this locus. Fine-mapping of the PSORS5 region revealed both point-wise and haplotype associations that might contribute to psoriasis susceptibility. The only gene within this region was also slightly less expressed in skin biopsies from psoriasis plaque than from control individuals. Further genotyping studies are needed to relate the expression data to the associating genotypes, before a disease susceptibility allele can be identified.
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