Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis
Background The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case–control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect.
Objectives As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis.
Methods We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test.
Results The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0·753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0·026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0·000 27 for allele 4 in the same study group.
Conclusions In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.
Document Type: Research Article
Affiliations: 1: Department of Dermatology, Medical School Charité, Humboldt University, Berlin and Research Business Area Dermatology, Schering AG, Berlin, Germany 2: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany 3: Institute of Human Genetics, University of Erlangen-Nürnberg, Erlangen, Germany 4: Fachklinik Bad Bentheim, Bad Bentheim, Germany 5: Department of Public Health and Clinical Medicine, Section for Dermatology and Venereology, Umea University, Umea, Sweden 6: Department of Dermatology, University of Münster, Münster, Germany
Publication date: August 1, 2003