HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis

Abstract

Background: Psoriasis vulgaris is an immune-mediated inflammatory skin disease. Although the pathogenesis of psoriasis is unclear, genetic susceptibility, such as HLA-C*06:02, is believed to be a major risk factor. However, there is a paucity of knowledge regarding the relationship between genetics and the response to systemic treatment of psoriasis. We hypothesized that genetic variations in human leukocyte antigen (HLA) genes may act as predictors of acitretin treatment in psoriasis. The aim of our study was to explore the presence of HLA gene variants in patients with moderate-to-severe psoriasis receiving acitretin treatment. Methods: A total of 100 Han Chinese patients with psoriasis completed the study. 24 patients including 16 responders and 8 non-responders underwent deep sequencing by MHC targeted region capture and 76 samples were genotyped by Sanger sequencing (SBT) based HLA typing for validation. Results: Regressions with adjustment for age, sex, body mass index (BMI), and baseline psoriasis area and severity index (PASI) revealed that two HLA alleles (HLA-DQA1*:02:01, DQB*:02:02) were associated with the response to acitretin. The DQA1*0201-positive patients showed a better response to acitretin compared to the DQA1*0201-negative patients (relative risk (RR) = 10.34, 95% confidence interval (CI): 2.62-40.77, p = 0.001), and the DQB1*0202-positive patients manifested a better response to acitretin when compared to the DQB1*0202-negative patients (RR = 21.01, 95% CI: 2.53-174.27, p = 0.005). Conclusions: Our observations support the potential role of HLA-DQA1*:02:01 and DQB*:02:02 as pharmacogenetic markers of the acitretin response in patients with psoriasis.

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

“…In the present study, the following 92 novel genomic markers for psoriasis were identified through GWAS and PRS ( Table SI ). Additionally, 61 previously reported genomic markers associated with psoriasis in Taiwanese populations were identified ( Table SI ): ATP binding cassette subfamily F member 1 ( 47 ), advanced glycosylation end-product specific receptor ( AGER ) ( 48 ), allograft inflammatory factor 1 ( 49 ), Annexin A6 ( 50 ), butyrophilin-like 2 ( BTNL2 ) ( 51 ), complement C2 ( 52 ), chromosome 6 open reading frame 15 ( 53 , 54 ), complement factor B ( 52 , 55 ), fibroblast activation protein α ( 56 ), HLA complex group 26 ( 57 ), HLA complex group 27 ( 57 ), HLA complex group 9 ( 58 ), HLA complex P5 ( 59 , 60 ), HLA complex P5B ( 59 , 60 ), major histocompatibility complex, class I, A ( HLA-A ) ( 61 ), major histocompatibility complex, class I, B ( HLA-B ) ( 62 , 63 ), major histocompatibility complex, class I, C ( HLA-C ) ( 53 , 54 ), major histocompatibility complex, class II, DM β ( HLA-DMB ) ( 64 ), major histocompatibility complex, class II, DQ α1 ( HLA-DQA1 ) ( 65 ), major histocompatibility complex, class II, DQ α2 ( HLA-DQA2 ) ( 66 ), major histocompatibility complex, class II, DQ β1 ( HLA-DQB1 ) ( 67 ), major histocompatibility complex, class II, DR β1 ( HLA-DRB1 ) ( 67 ), major histocompatibility complex, class I, E ( HLA-E ) ( 68 ), major histocompatibility complex, class I, F ( HLA-F ) ( 69 ), major histocompatibility complex, class I, G ( HLA-G ) ( 70 ), heat shock protein family A ( Hsp70 ) member 1A ( HSPA1A/HSPA1B ) ( 71 ), Hsp70 member 1-like ( ...…”

“…The antigenic peptides contained in each HLA molecule are unique, despite some overlap in binding specificities ( 111 , 112 ). Certain HLA alleles, such as HLA-A ( 61 ), HLA-B ( 62 , 63 ), HLA-C ( 53 , 54 ), HLA-DMB ( 64 ), HLA-DQA1 ( 65 ), HLA-DQA2 ( 66 ), HLA-DQB1 ( 67 ), HLA-DRB1 ( 67 ), HLA-E ( 68 ), HLA-F ( 69 ) and HLA-G ( 70 ), are more prevalent in patients with psoriasis. The findings of the present study indicated a significant association between the genetic variability of HLA -related genes located on chromosome 6 and the development of psoriasis.…”

Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review

“…Among 100 Chinese individuals, those who were positive for the DQA10201 allele demonstrated a more favorable response to acitretin compared to those who were negative for the same allele. (PASI75 at 2 months, p = 0.001) [ 37 ].…”

“…HLA-DQB1 alleles have been mentioned to involve in genetic predisposition to psoriasis vulgaris in the Slovak population [ 38 ]. In 100 Chinese patients, the DQB1*0202 -positive patients showed a better response to acitretin than the DQB1*0202 -negative patients (PASI75 at 2 months, p = 0.005) [ 37 ].…”

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

“…Contradictory results have been received regarding the association between the VEGFA rs833061 variant and acitretin response with a similar sample size [ 46 , 47 ], while negative results were reported regarding APOE [ 48 ] and IL36RN [ 49 ] SNPs, implying the assessment of patient subgroups according to additional disease-associated loci. Indeed, deep sequencing of the HLA locus uncovered several loci associated with the treatment response (n = 24), with the HLA-DQA1*:02:01, DQB*:02:02 showing the same association signals in the validation set (n = 76) [ 50 ]. Variants mapped to ion transporters were also documented to discriminate acitretin responsiveness of 151 Chinese Han psoriasis patients, while functional experiments showed that the SLCO1B1 rs4149056 C allele reduced the acitretin uptake, resulting in improved treatment efficacy [ 51 ].…”