A Large-Scale, Stratified Genetic Analysis of the Major Histocompatibility Complex Region in Early- and Late-Onset Psoriasis in China

Abstract

Background Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP; <40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C * 06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods We first calculated the MHC-based heritability of EOP and LOP respectively. Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previous study. Results We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%). Further association analysis identified three independent loci (HLA-C * 01:02, p =6.70×10 −8 ; HLA-A amino acid position 9, p =3.27×10 −17 ; and HLA-A amino acid position 161, p =5.75×10 −10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C * 06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C * 06:02-positive psoriasis patients have earlier onset. Conclusion Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe Psoriasis

“…To evaluate the levels of serum lipids in patients with psoriasis with different phenotypes and the change after MTX treatment, we first characterized the serum lipid profiles of 96 patients with psoriasis and further identified the differentially expressed lipids between EOP and LOP. Some previous studies have shown that EOP and LOP differ in their clinical characteristics and genetic background [ 5 , 17 , 18 ]. By comparing the serum lipid metabolites in LOP and EOP, we found that the levels of DG (16: 1/18: 1) and DG (18: 1/18: 1) significantly increased in EOP.…”

Correlation of HLA-Cw6 Positivity with Clinical Characteristics and Treatment Efficacy in Korean Patients with Psoriasis

“…Also, HLA-Cw6 positivity is known to be related to stress, obesity 6 , and guttate psoriasis 7 . In addition, patients carrying the allele are more likely to have arm, leg, and trunk involvement, along with the Koebner phenomenon 8 . Several studies involving Caucasian and Chinese patients have shown HLA-Cw6-positive patients to be more responsive to methotrexate 9 and ustekinumab 6 10 11 12 ; HLA-Cw6 positivity also tends to be less frequent in high-need patients, who fail conventional therapy 11 .…”

Dactylitis and Early Onset Psoriasis in Psoriatic Arthritis: Are they Markers of Disease Severity? A Clinical Study

“…A recent analysis in PsO patients confirmed that HLA alleles explain a larger heritability of EOP, moving towards a genetic profiling to predict the PsO risk of a more severe phenotype [ 5 ]. The PsO stratification age among PsA patients was also assessed, showing that it could play a role in the clinical and genetic features of PsA patients [ 6 , 7 ].…”