Improving the long-term efficacy of TNF- monoclonal antibodies can reduce the incidence of cardiovascular events and mortality (Hugh et al., 2014; Rubbert-Roth et al., 2019). to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF- biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), Osthole and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is usually attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (2 = 6.577, = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNF monoclonal antibody. Patients with the genotype of TG (2 = 6.124, = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (2 = 7.664, = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics. = 0.022), and the T allele showed a higher frequency in the psoriasis populace (= 0.036). The allele and genotype frequencies of the other five SNPs Osthole (rs6887695, rs4819554, rs763780, rs11209032, and rs2201841) were not statistically associated with psoriasis susceptibility (Table 2). None of the selected SNPs was found to be associated with the severity and type of psoriasis (Table 3). TABLE 1 The demographics data of psoriasis patients and controls. = 0.02) between the effective group (T&A) keratin7 antibody and the non-effective group (T&A). The frequency of AA genotype in the effective group (T&A) was higher than that in the noneffective group (66.7%). No correlation between rs11209032 and the efficacy was found in patients who used acitretin only, so the effect of this SNP around the sensitivity of acitretin was excluded. Moreover, in patients treated with acitretin alone (A), the SNP (rs3212227, 2 = 6.124, = 0.035) at the IL-12b was significantly different between the effective group and the non-effective group. The frequency of the TG (50.0%) genotype was significantly higher than that of the GG (16.7%) genotype in the effective group (A). The frequency of the GG (72.20%) genotype in the non-effective group (A) was significantly higher than that of the TG (11.1%) genotype. The other SNPs were not found to be associated with the efficacy of acitretin alleviating SNR or acitretin alone (Table 4). TABLE 4 Comparison of the relationship between each SNP and the efficacy of acitretin alone or the efficacy of acitretin treating secondary non-response to TNF-a biological agents. = 0.022), and T allele also showed a higher frequency in the psoriasis population (= 0.036) (2 = 6.317, = 0.048). IL-12 and IL-23 play important roles in the pathogenesis of psoriasis by sharing the p40 subunit required for binding to their receptors which have been shown to be overexpressed in psoriatic lesions. IL-12 and IL-23 can induce cells to differentiate into Th1/Th17, thereby increasing the production of pro-inflammatory cytokines, including IL-17A, IL-17F, IL-22, IL-26, IFN-, CCL20, and TNF-(Jeon et al., 2017). In addition, the role of interleukin 12/23p40 cytokines in psoriasis and other inflammatory diseases is also supported by the effectiveness of interleukin 12/23?mAb therapy (Eiris et al., 2012). Rs11209032 has been shown to be associated with many diseases, including psoriasis, Behcets disease, and ankylosing spondylitis and is related to the efficacy of immunotherapy in aplastic anemia (Jiang et al., 2010; Roberts et al., 2016; Zhao et al., 2018). Rs3212227 has been extensively studied in diseases (for example, rheumatoid arthritis (Shen et al., 2015), cervical cancer (Chen et al., 2009)) and the possibility of being a relevant marker of prognosis has been proposed Osthole in different tumors (Cerhan et al., 2007; Yuzhalin and Kutikhin, 2012). Therefore, this study suggested that rs11209032(IL-23R) and rs3212227(IL-12B) may be used as genetic biomarkers for clinic use. In patients with psoriasis, the genotype of rs11209032 can be detected to determine whether acitretin is suitable to reduce the SNR and the genotype of rs3212227.