**5.2 FOXP3**

FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent reports have shown the FOXP3 SNPs contribute to the susceptibility to some autoimmune and autoinflammatory disorders. The FOXP3 SNP rs3761548 (-3279 C/A) was significantly associated with BD in the Iranian patients [113]. The FOXP3 (-3279 C/A) A allele has been reported to be associated with neural involvement in BD in Egyptian patients [114]. A low copy number variant of the FOXP3 gene was shown to increase risk in female BD patients in a Chinese cohort [115].

#### **5.3 FUT2**

FUT3 (Fucosyltransferase) gene is responsible for the formation of histo-blood group antigens, it might affect the intestinal microbiota composition and modulate innate immune responses [116]. Recent studies indicated that the association between the FUT2 gene variants (rs632111, rs601338, rs602662, rs492602, rs681343, and rs281377) and BD was reported in Iranian and Turkish populations [117].

#### **5.4 ACE and VEGF**

The renin-angiotensin system (RAS) is important in vascular tone and inflammatory processes. It has been suggested that DD genotype of ACE gene I/D polymorphism might be a genetic marker for BD in Turkish populations [118, 119]. In the other hand, the ACE gene I/D polymorphism was not associated with BD patients in

a Iranian cohort and in an another Turkish population [120, 121]. VEGF is a potent angiogenic factor exhibiting various endothelial cell effects, including endothelial cell survival, proliferation, migration and tube formation, and also acts as a proinflammatory cytokine [122, 123]. The carriers of the -634C (3'untranslated region UTR) and I (insertion/deletion) alleles of VEGF gene were associated with a susceptibility to BD in Italian patients [124].
