Background: Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control.
Objectives: To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population.
Methods: We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method.
Results: We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132).
Conclusions: Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.