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TNF polymorphisms in psoriasis: Association of psoriatic arthritis with the promoter polymorphism TNF*‐857 independent of the PSORS1 risk allele
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Personen und Körperschaften: | , , , , , , , , , |
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Titel: |
TNF polymorphisms in psoriasis: Association of psoriatic arthritis with the promoter polymorphism TNF*‐857 independent of the PSORS1 risk allele |
In: | Arthritis & Rheumatism, 56, 2007, 6, S. 2056-2064 |
veröffentlicht: |
Wiley
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Umfang: | 2056-2064 |
ISSN: |
0004-3591 1529-0131 |
DOI: | 10.1002/art.22590 |
Zusammenfassung: | <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Single‐nucleotide polymorphisms (SNPs) of the tumor necrosis factor gene <jats:italic>TNF</jats:italic> at positions −238 and −308 have been associated with psoriasis vulgaris and psoriatic arthritis (PsA). The strong linkage disequilibrium (LD) at chromosome region 6p21, a region known to harbor risk factors for psoriasis susceptibility (<jats:italic>PSORS1</jats:italic>) other than just SNPs of the <jats:italic>TNF</jats:italic> gene, renders the interpretation of these findings difficult. The aim of this study was to analyze several SNPs of the <jats:italic>TNF</jats:italic> gene and its neighboring <jats:italic>LTA</jats:italic> gene for independent and dependent carriage of the <jats:italic>PSORS1</jats:italic> risk allele.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>SNPs in the promoter of the <jats:italic>TNF</jats:italic> (−238G/A, −308G/A, −857C/T, and −1031T/C), <jats:italic>LTA</jats:italic> (+252A/G), <jats:italic>TNLFRSF1A</jats:italic> (+36A/G), and <jats:italic>TNLFRSF1B</jats:italic> (+676T/G) genes were genotyped in 375 psoriasis patients, 375 PsA patients, and 376 controls. The Trp‐ Trp‐Cys‐Cys haplotype of the <jats:italic>CCHCR1</jats:italic> gene (<jats:italic>CCHCR1</jats:italic>*<jats:italic>WWCC</jats:italic>) was used as an estimate of the risk allele <jats:italic>PSORS1</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Whereas we were able to confirm the previously described strong association of allele <jats:italic>TNF</jats:italic>*‐<jats:italic>238A</jats:italic> with psoriasis, our study revealed that this association was completely dependent on carriage of the <jats:italic>PSORS1</jats:italic> risk allele. For PsA, but not psoriasis vulgaris without joint involvement, a strong association with the allele <jats:italic>TNF</jats:italic>*‐<jats:italic>857T</jats:italic> (odds ratio 1.956 [95% confidence interval 1.334–2.881]; corrected <jats:italic>P</jats:italic> = 0.0025) was also detected in patients negative for the <jats:italic>PSORS1</jats:italic> risk allele.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results indicate that there are genetic differences between psoriasis vulgaris patients with and without joint manifestations. While the previously reported association between <jats:italic>TNF</jats:italic>*‐<jats:italic>238A</jats:italic> and psoriasis seems to primarily reflect LD with <jats:italic>PSORS1</jats:italic>, <jats:italic>TNF</jats:italic>*‐<jats:italic>857T</jats:italic> may represent a risk factor for PsA that is independent of the <jats:italic>PSORS1</jats:italic> allele.</jats:p></jats:sec> |
Format: | E-Article |
Quelle: | Wiley (CrossRef) |
Sprache: | Englisch |