Tumour necrosis factor‐α polymorphism as one of the complex inherited factors in pemphigus

Abstract

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus.

Genetic factors in pemphigus

“…In a study performed in a large series of patients with Brazilian endemic pemphigus and controls, no associations were found between LTA/ or TNF/ single nucleotide polymorphism (SNP) and PF indicating that genetic variability of these loci does not participate in susceptibility/ resistance to the disease [98]. However, in an association study involving a limited number of PF patients, a positive association of TNFa promoter gene polymorphism with sporadic PF was observed [99]. Polymorphisms of TAP1 and TAP2 genes that are located in the HLA class II locus and that encode for the transporters associated with antigen processing (TAP) molecules were recently analyzed in Japanese pemphigus patients but no association was found with the disease [100].…”

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus

“…No associations were found between LTA or TNF single nucleotide polymorphism (SNP) and Brazilian endemic PF, indicating that genetic variability of these loci does not contributed to susceptibility/resistance to the disease [6]. However, while another study showed a positive association of TNFa (À308 G/A) promoter gene polymorphism with sporadic PF [7]. Our previous study showed no significance between the disease and the rs10818488 G/A, located in the intergenic region between the complement C5 and TRAF1 gene ''TNF receptor associated factor'' gene, nor with the C5 sera levels which could strengthen the secondary role of complement in the PF [8].…”

The role of T cells in cutaneous autoimmune disease

“…Additionally, abnormal expression of IL-6 and TNF-a has been detected in the lesional epidermis of FS patients [81] and a TNFa gene promoter polymorphism has been identified in association with FS [82] underscoring the pivotal role of cytokines in directing disease development.…”