Vitiligo is the most common depigmenting disease characterized by achromic macules [32]. The exact mechanism of vitiligo pathogenesis is still not fully understood. A primary defect in melanocytes is suggested, however, inflammation and autoimmunity plays an important role [3]. Among the biological functions of melanocytes is cytokine production with the consequent development of an immune response [3]. The role of cytokines in vitiligo has been evaluated in multiple studies, which report significantly higher expression of pro-inflammatory cytokines and its participation in the depigmentation process on vitiligo [33, 34]. In addition, different studies have established that genetic factors are associated with the susceptibility of developing vitiligo. Genome-wide association studies have discovered more than 40 susceptible loci that are associated with different pathways of vitiligo pathogenesis [35]. Some mutated genes associated with depigmentation mechanisms in vitiligo include MITF, POMC, DCT, TYRP1, MLANA, and CAPN3 [1]. Other downregulated genes that are associated with the loss of melanocyte homeostasis include LEF1, p38 MAPK, PI3KCB, RPS6KB1, Bcl‑2, and USF1 [1]. Many of these genes, such as PTPN22, IFIH1, CLNK, BACH2, CCR6, FGFR1OP, and ZMIZ1 among multiple others, are involved in other autoimmune diseases [35]. On the other hand, multiple studies have investigated the association of some polymorphisms and the susceptibility of developing vitiligo [26, 35]. In our literature search, several polymorphisms were found: (1) NLRP-1 (rs2670660) [36], TNF-α (rs1800629) [27, 37–39], IL-4R (rs1801275) [40], CAT − 89 A/T (rs7943316), 389 C/T (rs769217), and 419 C/T (rs11032709) [41], LXR-α (rs11039155 and rs2279238) [42], PTPN22 (rs2476601) [43], TNFB (rs909253) [44], IFIH1 (rs1990760) [45], and MTHFR (rs1801131 and rs1801133) [46].
Emerging evidence supports a pivotal role for IL-17 in vitiligo pathogenesis via different pathways, including those involved in chemotactic activity and secretion of pro-inflammatory cytokine, such as IL-6 and TNF-α, which have an effect on melanocyte destruction in vitiligo [47]. IL-17 has already been proven to be related to multiple inflammatory and autoimmune diseases [22]. IL-17F (7488 A/G) contributes to neutrophil recruitment and activation through cytokine stimulation [48]. The mutated variant of this polymorphism is responsible for a histidine to arginine substitution at amino acid 161, leading to a change in the conformation of IL-17F [49]. In previous studies, this genetic variant has been associated with digestive system neoplasms, especially gastric cancer [28, 50], rheumatoid arthritis [6, 48, 51–53], Crohn’s disease [54], asthma [55], osteoarthritis [56–59], psoriasis [60], immune thrombocytopenia [61], cervical cancer [62, 63], systemic lupus erythematosus [64], and hepatitis B virus infection [65]. On the other hand, the IL-17A rs2275913 (-197G/A) SNP includes the substitution of guanine for adenine in the 197th nucleotide position upstream of the starting codon of the IL17A gene, and it is located within a binding motif for the nuclear factor of activated T-cells (NFAT), which affects production of IL-17 from T-cells. Therefore, this mutation has an important role in allergic, autoimmune, and infectious diseases [66, 67]. Its genetic analysis found no association between this genotype and vitiligo (χ2 = 0.686; P = 0.71), and the analyzed anthropometric parameters. For IL-17A rs4711998 (-832A/G), some studies have associated it with asthma [68], chronic hepatitis B, and hepatitis B virus-related liver cirrhosis [69, 70]. Its genetic analysis found no association between this genotype and vitiligo (χ2 = 1.724; P = 0.422) and the analyzed anthropometric parameters.
Given the uncertainty of whether the variants in the IL-17 gene may modulate susceptibility to vitiligo development, the aim of the current study was to determine the association of genetic variants in IL-17A and IL-17F genes with vitiligo development. To our knowledge, this study is the first correlating polymorphisms of IL-17 with vitiligo in a Mexican population. The close association of SNP rs763780 (7488 A/G) with vitiligo susceptibility is the most important finding of this study and this SNP could be considered as a risk factor for the development of vitiligo in Mexican patients. The combination of GG/GA alleles of rs763780 (7488A/G) is strongly associated with an increase in disease risk in our population with a frequency of 63.79% in cases compared with 45.68% in controls (P = 0.0056, OR = 2.0943, 95%CI = 1.2375–3.5445). This finding suggests that this allelle can serve as a marker for the prediction vitiligo susceptibility. Some potential limitations of our study include the sample patient size; thus, our results must be interpreted with caution. Another important aspect is that our entire group of patients with vitiligo was from a specific region of our country. The ethnic heterogeneity may influence susceptibility to vitiligo or clinical phenotypes. In addition, the SNP rs763780 (7488A/G) must be further studied to elucidate its role in vitiligo development of vitiligo. Therefore, to determine the association of IL-17 polymorphisms with vitiligo, larger scale studies not only from our region, but also from the rest of Mexico, are needed. Much work remains to be done to clarify all aspects of the pathogenesis of this complex disease. In conclusion, IL-17F rs763780 (7488A/G) appears to be associated with an increase in the risk of vitiligo development in the Mexican population.