The exact etiology of BD remains elusive, but genetic factors play essential roles [20]. Genome-wide association studies have suggested that special genetic variants might predispose individuals to autoimmune diseases like BD [21–24]. The possible roles of leptin and adiponectin gene polymorphisms in the pathogenesis of multiple sclerosis, coronary artery disease, diabetes mellitus, and atopic dermatitis have been well-indicated [16, 25–27]. Here, the possible associations between adiponectin and leptin gene variants, as well as their serum levels and BD were evaluated among Iranians. Our results proved several associations between leptin gene variants rs7799039 and rs2167270 and BD susceptibility and its clinical manifestation but no significant associations were found between adiponectin SNPs rs1501299 and rs266729 and BD.
We indicated that the frequencies of leptin rs7799039AG and GG genotypes and rs7799039G allele, as well as G allele carriers (AG + GG), were significantly more in BD patients compared to healthy individuals. After gender stratification, all the results remained significant in males except for the AG genotype that remained significant in females. Of interest, genital aphthous had a significantly lower frequency in male patients carrying AG genotype. These results probably indicate the protective role of the A allele in male individuals. Furthermore, carriers of the G allele had a greater risk of BD among men and may suggest the G allele as a risk allele for BD development in males.
We found that patients had significantly more rs2167270AG, AG + AA genotypes, and rs2167270A allele compared to healthy subjects. Of note, genital aphthous was more frequently seen in patients carrying rs2167270AA genotype and rs2167270A allele. After gender stratification, these results remained significant in female patients. It can be suggested that the A allele carriers were associated with increased risk of BD and may point to a role for this genotype in BD development. Few studies have focused to assess the correlation between leptin polymorphisms and BD risk. In contrast to our study, Aydin et al. found no significant relationship between leptin gene polymorphism and the incidence and clinical manifestation of BD [28]. A study by Okudan et al. has also shown no significant correlation between the oligopolymorphic codon 25 (CAA/CAG) of leptin, serum level of leptin, and BD [29]. Such discrepancies between our findings and others might be due to the differences in ethnicity, environmental factors which probably affect gene expression, clinical heterogeneity, and small sample size.
For the first time, we examined the possible associations between rs1501299 and rs266729 of adiponectin gene and BD susceptibility. However, no significant association was found between these SNPs and BD that confers these genetic variants might not be involved in BD susceptibility. Our data also revealed significantly elevated serum levels of adiponectin in BD patients but leptin levels were not statistically different between patients and healthy subjects. Several studies have indicated increased serum levels of adiponectin in the case of autoimmune diseases [30, 31]. In such situations, adiponectin might aggravate or attenuate the inflammation [11, 32, 33] hence, more investigations are needed to address the precise role of adiponectin in BD patients. Additionally, we indicated that those patients with genital aphthous had significantly elevated levels of leptin but previous reports have shown such a situation in BD patients compared to healthy subjects [29, 34]. Elevated levels of leptin have also been shown in the active form of BD and patients with longer disease duration [34]. Our results need to be confirmed by functional studies and further studies using larger sample sizes are needed to verify our results.