Identification of PTPN22,ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

Abstract

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10 , OR=5.07), rs16861329 on 3q27.3 (P=2.02×10 , OR=0.87) and rs849135 on 7p15.1 (P=6.59×10 , OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T-cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.

Psoriasis and Cardiovascular Risk: A Comprehensive Review

“…However, other mechanisms have been proposed to explain this association. Genetically, several genes (CDKAL1, PTPN22, ST6GAL1, JAZF1) have been linked to both type 2 diabetes and psoriasis [42,43]. Additional emerging pathways that are implicated include those of the glucagon-like peptide-1 receptor and the incretin effect [44,45].…”

Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s

“…The weighted GRS was calculated on the basis of the 50 SNPs by using a previously described weighted method . Each SNP was weighted by β coefficients obtained from published meta‐analyses . (The original β coefficients can be found in the references listed in Table S2.)…”

“…3 Each SNP was weighted by β coefficients obtained from published metaanalyses. 4,7,[10][11][12]16,17,[24][25][26][27][28][29][30][31][32][33][34][35] (The original β coefficients can be found in the references listed in Table S2.) The weighted GRS was calculated by multiplying each β coefficients by the number of corresponding risk alleles and summing the products, then dividing the sum by twice the sum of the β coefficients and multiplying by 50.…”

Translational drug discovery and development with the use of tissue‐relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy

“…In this context, it may be worth mentioning that in a case report a female patient was described who was affected by both Crohn's disease and psoriasis and who was given a single dose of infliximab as treatment for Crohn's disease. [31,32] In the final stages of preclinical drug development, it becomes imperative to have access to transgenic animals and knock-in and knockout animals to reflect the human metabolic situation and to use human tissues for primary assays. [28] Contemplating the geometry of bispecific antibodies that have been designed so far, it is imaginable that the shape of things to come in the future may be antibodies or other modalities that bind to three or four targets, depending on their intended therapeutic purpose and depending on the pathways that they will be intended to interfere with.…”