Association Analysis of IL10, TNF-α, and IL23R-IL12RB2 SNPs with Behçet’s Disease Risk in Western Algeria

Abstract

Objective: We have conducted the first study of the association of interleukin (IL)-10, tumor necrosis factor alpha (TNF-α), and IL23R-IL12RB2 region single nucleotide polymorphisms (SNPs) with Behçet’s disease (BD) in Western Algeria.Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct sequencing for 11 SNPs including 2 SNPs from the IL10 promoter [c.-819T > C (rs1800871), c.-592A > C (rs1800872)], 6 SNPs from the TNF-α promoter [c.-1211T > C (rs1799964), c.-1043C > A (rs1800630), c.-1037C > T (rs1799724), c.-556G > A (rs1800750), c.-488G > A (rs1800629), and c.-418G > A (rs361525)], and 3 SNPs from the IL23R-IL12RB2 region [g.67747415A > C (rs12119179), g.67740092G > A (rs11209032), and g.67760140T > C (rs924080)].Results: The minor alleles c.-819T and c.-592A were significantly associated with BD [odds ratio (OR) = 2.18; 95% confidence interval (CI) 1.28–3.73, p = 0.003]; whereas, there was weaker association between TNF-α promoter SNPs or IL23R-IL12RB2 region and disease risk.Conclusion: Unlike the TNF-α and the IL23R-IL12RB2 region SNPs, the two IL10 SNPs were strongly associated with BD. The -819T, and -592A alleles and the -819TT, -819CT, and -592AA and -592CA genotypes seem to be highly involved in the risk of developing of BD in the population of Western Algeria.

Genetics of Behçet’s Disease

“…A significant association (reaching a GWAS p value) of the IL-23R gene with BD was found at the SNP rs11209026 (Gly149Arg) in Japanese, and at the SNP rs76418789 (Arg381Gln) in Turkish cohort [61]. The association between BD and the IL-23R/IL-12RB2 genes appeared to be consistent in multiple reports with different populations including Turkey [52], Japanese [53], Han Chinese [62,63], Iranian [64], Western Algeria [65], and Korean [66].…”

Are neutrophilic dermatoses autoinflammatory disorders?

“…However, BD is now regarded as one of the major autoinflammatory diseases . The genetic association of BD with human leucocyte antigen‐B51 explains only 20% of the disease heritability, and a polygenic origin of this disorder has been shown by genome‐wide association studies, revealing variants in the genes ERAP1 , IL10 , IL23R , CCR1 , STAT4 , KLRC4 and IL12A . The fact that BD is characterized by hyperactive neutrophils and recurrent episodes of neutrophilic inflammation, without a causative autoantigen or respective autoantibodies, opened up the possibility that BD may be an autoinflammatory disease and that IL‐1 may also be involved in its pathogenesis.…”

“…39,80,81 The genetic association of BD with human leucocyte antigen-B51 explains only 20% of the disease heritability, 82 and a polygenic origin of this disorder has been shown by genome-wide association studies, revealing variants in the genes ERAP1, IL10, IL23R, CCR1, STAT4, KLRC4 and IL12A. [83][84][85][86][87][88][89] The fact that BD is characterized by hyperactive neutrophils and recurrent episodes of neutrophilic inflammation, without a causative autoantigen or respective autoantibodies, opened up the possibility that BD may be an autoinflammatory disease and that IL-1 may also be involved in its pathogenesis. Indeed, elevated levels of IL-1b have been reported in BD, 90 and excellent clinical responses have been reported in BD and BD-associated uveitis with IL-1-targeted therapy.…”

Investigation of the association of Vogt–Koyanagi–Harada syndrome with IL23R-C1orf141 in Han Chinese Singaporean and ADO-ZNF365-EGR2 in Thai

“…A report from Japan suggested that the IL23R gene was associated with autoimmune thyroid diseases (AITDs), but that this was restricted to a specific ethnic group 21. Previous studies have shown a stronger association of IL23R with Behcet’s disease in patients from Turkey22 as compared with cases from Algeria 23. Two SNPs located in the second haplotype block of the IL23R gene showed a marginal association with the risk of polyarticular psoriatic arthritis (p=0.05) in a Romanian case–control cohort 24.…”