**5.6 SUMO4**

Small ubiquitin-like modifier 4 (SUMO4) has been shown to have the potential to down-regulate NF-kappaB signal, leading to decreased transcription of pro-inflammatory cytokines [130, 131]. The association between the SUMO4 gene (rs237024 and rs237026) polymorphisms and BD was first reported in a Chinese cohort, and they showed the GGAC haplotype was protectively associated with BD in HLA-B51 positive patients [132]. The association was replicated in Tunisian and Korean cohorts for the rs237024 and rs237026 polymorphisms of SUMO4 gene. This study also showed this polymorphisms were associated with disease severity and also some clinical manifestations such as skin lesions, and vascular involvement [133, 134].
