Interleukin-10 promoter polymorphism in psoriasis

被引:41
作者
Asadullah, K
Eskdale, J
Wiese, A
Gallagher, G
Friedrich, M
Sterry, W
机构
[1] Humboldt Univ, Med Sch Charite, Dept Dermatol, Berlin, Germany
[2] Univ Glasgow, Glasgow Royal Infirm, Dept Surg, Glasgow G31 2ER, Lanark, Scotland
关键词
cytokines; genetic; interleukins; polymorphism; psoriasis;
D O I
10.1046/j.1523-1747.2001.01350.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Beneficial effects of interleukin-10 therapy and lower endogenous interleukin-10 formation compared with atopic dermatitis and cutaneous T cell lymphomas indicated that interleukin-10 is a key cytokine in psoriasis, The interleukin-10 promoter is highly polymorphic, with two informative microsatellites, interleukin-10.G and interleukin-10.R. In order to understand whether interleukin-10 itself is a predisposing gene for the psoriasis susceptibility we analyzed interleukin-10 promotor polymorphism in patients. The distribution of interleukin-10.G and interleukin10.R microsatellite alleles did not vary between patients (n = 78) and healthy controls (n = 80). In addition, when the psoriasis patients were stratified according to age of onset (younger than 40 y of age, or age 40 and older), no difference in allele distribution was observed; however, a clear differential distribution was revealed at the interleukin10.G locus when patients were stratified according to whether they had a positive family history of psoriasis (p = 0.04). This difference was due to an over-representation of the interleukin10.G13 allele in those patients with familial disease (40.4% vs 19.6%, Chi-square = 7.292, p = 0.007). The positive association of allele interleukin10.G13 with familial psoriasis was especially true when patients with an early onset (< 40 y of age) of the disease were compared with those patients with early onset against a nonfamilial background (39.6% vs 14.5%. Chisquare = 8.959, p = 0.003). Patients with age-of-onset of less than 40 were 4-fold [odds ratio = 3.85 (1.55-9.62)] more likely to have a psoriatic family background if they carried this interleukin10.G13 allele. These data suggest that the interleukin-10 locus contributes to the heritability of psoriasis susceptibility.
引用
收藏
页码:975 / 978
页数:4
相关论文
共 30 条
[1]   IL-10 is a key cytokine in psoriasis -: Proof of principle by IL-10 therapy:: A new therapeutic approach [J].
Asadullah, K ;
Sterry, W ;
Stephanek, K ;
Jasulaitis, D ;
Leupold, M ;
Audring, H ;
Volk, HD ;
Döcke, WD .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (04) :783-794
[2]   Interleukin 10 treatment of psoriasis -: Clinical results of a phase 2 trial [J].
Asadullah, K ;
Döcke, WD ;
Ebeling, M ;
Friedrich, M ;
Belbe, G ;
Audring, H ;
Volk, HD ;
Sterry, W .
ARCHIVES OF DERMATOLOGY, 1999, 135 (02) :187-192
[3]  
Asadullah K, 1999, BRIT J DERMATOL, V141, P94
[4]   Interleukin-10 in cutaneous disorders:: implications for its pathophysiological importance and therapeutic use [J].
Asadullah, K ;
Sabat, R ;
Wiese, A ;
Döcke, WD ;
Volk, HD ;
Sterry, W .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 1999, 291 (12) :628-636
[5]   Cytokine gene polymorphism in human disease: on-line databases [J].
Bidwell, J ;
Keen, L ;
Gallagher, G ;
Kimberly, R ;
Huizinga, T ;
McDermott, MF ;
Oksenberg, J ;
McNicholl, J ;
Pociot, F ;
Hardt, C ;
D'Alfonso, S .
GENES AND IMMUNITY, 1999, 1 (01) :3-19
[6]   CORRELATED INCREASES OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-6 AND GRANULOCYTE-MONOCYTE COLONY-STIMULATING FACTOR LEVELS IN SUCTION BLISTER FLUIDS AND SERA OF PSORIATIC PATIENTS - RELATIONSHIPS WITH DISEASE SEVERITY [J].
BONIFATI, C ;
CARDUCCI, M ;
FEI, PC ;
TRENTO, E ;
SACERDOTI, G ;
FAZIO, M ;
AMEGLIO, F .
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 1994, 19 (05) :383-387
[7]   The pathogenesis of psoriasis: Immunological facts and speculations [J].
Bos, JD ;
De Rie, MA .
IMMUNOLOGY TODAY, 1999, 20 (01) :40-46
[8]   New polymorphisms in the IL-10 promoter region [J].
D'Alfonso, S ;
Rampi, M ;
Rolando, V ;
Giordano, M ;
Momigliano-Richiardi, P .
GENES AND IMMUNITY, 2000, 1 (03) :231-233
[9]  
D'Alfonso S, 2000, ARTHRITIS RHEUM, V43, P120, DOI 10.1002/1529-0131(200001)43:1<120::AID-ANR15>3.0.CO
[10]  
2-3