Identification of susceptibility SNPs in IL10 and IL23R-IL12RB2 for Behçet's disease in Han Chinese

Background Although previous genome-wide association studies in various cohorts have identified several susceptibility loci underlying Behcet's disease (BD), this has not yet led to a breakthrough in the management of BD. Objective This study aimed to further investigate the association of 26 candidate single nucleotide polymorphisms with previous genome-wide association studies–identified nearly positive P values (5.0 × 10 −8 P −5 ) in Chinese Han patients with BD. Methods A case-control association study was performed in 1206 patients with BD and 2475 healthy controls. Genotyping was performed using iPLEX Gold genotyping assay. Gene expression and cytokine production was quantified by real-time PCR and ELISA. Results The results showed that significantly higher frequencies of the IL23R-IL12RB2 /rs924080 TT genotype ( P  = 2.03 × 10 −8 ; odds ratio [OR] = 1.50), IL23R-IL12RB2 /rs12141431 CC genotype ( P  = 2.18 × 10 −8 ; OR = 1.53), IL10 /rs1800871 TT genotype ( P  = 5.88 × 10 −8 ; OR = 1.47), and IL10 /rs3024490 TT genotype ( P  = 2.80 × 10 −5 ; OR = 1.34) were found in BD. Functional experiments showed an increased IL23R expression and IL-17 production in rs12141431/CC genotype carriers compared with GG genotype carriers. A decreased IL10 expression and IL-10 production was observed in rs3024490/TT genotype carriers as compared with GG genotype carriers. Conclusions Our findings not only confirmed the association of IL10 /rs1800871 and IL23R-IL12RB2 /rs924080 with BD but also identified 2 susceptibility single nucleotide polymorphisms in IL10 and IL23R-IL12RB2 (rs3024490 and rs12141431) with BD in Han Chinese.