A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population

Abstract

Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis. In 208 patients and 266 normal controls, we analysed 31 single nucleotide polymorphisms in 12 genes (CAMP, IL17A, IL17F, IL17RA, IL22, JAK1, JAK2, JAK3, STAT3, TLR7, TLR9 and TYK2; abbreviations: CAMP, human cathelicidin antimicrobial peptide; STAT-3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TYK2, tyrosine kinase 2). Patients with psoriasis showed a strong association for IL17F rs763780 [odds ratio (OR) = 3·27, P = 0·04], which results in a histidine-to-arginine substitution, and JAK2 rs2274471 (OR = 2·66, P = 0·02). In addition, JAK2 rs7849191 showed a protective pattern, met the significance threshold (OR = 0·77, P = 0·05) and showed a tendency for an inverse association with the frequency of early-onset psoriasis under age 40 years (P = 0·07). In haplotype analysis, JAK1 rs310241A/rs2780889T showed a protective effect (OR = 0·73, P = 0·03) in psoriasis. In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population.

Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment (Review)

“…They demonstrated that the IL-17F polymorphism rs763780 T/C is strongly associated with psoriasis (1). The study found no association between the five evaluated polymorphism of IL-17RA or with the other evaluated polymorphisms and psoriasis (1).…”

“…IL-17F polymorphism rs763780 is strongly associated with psoriasis in Korean population (1), with a good response to treatment with infliximab and with no response to treatment with adalimumab or ustekinumab in Caucasian population (32). On the other hand, no association between this polymorphism and the disease was found in Japanese and Spanish population (4,16).…”

“…After activation, macrophages and dendritic cells produce IL-23 which play a mandatory role in differentiation of naïve CD4 + T cells into Th17 cells. This novel subset of Th17 cells produce IL-17A, IL-17F and IL-22, the main players in the formation of characteristic psoriasis lesions (1,13,15,16).…”

“…Psoriasis vulgaris is a chronic immune-mediated inflammatory disease with polygenic and multifactorial background and implies negative impact on the quality of life of psoriatic patients (1)(2)(3). The disease affects approximately 2-4% of the population (4,5), but several studies indicate that there are differences between Asia and other regions, with a lower incidence of psoriasis in Asians (0.3-1.2% in China) (6).…”

Genetic Signature of Acute Lymphoblastic Leukemia and Netherton Syndrome Co-incidence—First Report in the Literature

“…Majority of the detected somatic mutations, including our patient, involved the 683rd amino acid residue, which is an important amino acid for the JH2 domain-mediated negative autoregulation of JAK2 activity (32). The second somatic mutation associated with the JAK pathway regulation was a variant of interleukin-17 receptor (IL17RC) gene (33). Nucleoporin 214 (NUP214) is required for cell cycle and nucleocytoplasmic transport.…”