Comorbidity and clinical features of psoriasis vary according to HLA-C*06:02 status

A British cross-sectional investigation found that HLA-C*06:02-positive patients were more likely women and younger at diagnosis of psoriasis. Genetic effects on comorbid body weight were also different between the sexes [1].

Carrying the HLA-C*06:02 allele has been linked to certain features of psoriasis, such as early onset of disease, severe disease, guttate psoriasis, and differential response to therapy with biologics in the past [2–5]. “We, therefore, set out to systematically evaluate and further characterise differences between HLA-C*06:02 positive and negative psoriasis,” Dr Ravi Ramessur (King’s College London, UK) said [1]. To do so, data of people with European ancestry was analysed from 2 British cross-sectional databanks: the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) and the UK Biobank [1,2]. BSTOP is an observational study of severe psoriasis containing clinical and genotype data from more than 70 dermatology centres in the UK. The UK Biobank is a population-based biomedical research resource with also genotype and clinical data from questionnaires and healthcare records. In the BSTOP cohort (n=3,767), 43.5% were women, 53.7% were HLA-C*06:02 positive, and the median age of psoriasis onset was 20 years [1]. In contrast, the respective characteristics in the UK Biobank (n=5,519) were 45.7%, 46.3%, and 29 years of age.

“The 2 stand-out observations from our study were: firstly, intriguing sex-specific differences and, secondly, an association with comorbidity,” Dr Ramessur disclosed. In both datasets, HLA-C*06:02-positive participants were significantly more likely to be women and have a younger median age at onset of psoriasis (P<0.0001 for all). BSTOP also provided information on the proportion of those with a family history of psoriasis and this was considerably higher in carriers of the HLA-C*06:02 allele (60.2% vs 42.6%; P<0.0001).

Obesity and hypertension associated with negative HLA-C*06:02 status

HLA-C*06:02 negativity was also associated with higher levels of obesity in terms of waist circumference and BMI, an effect that was more pronounced in women.

Overall, comorbid cardiometabolic disease had a higher prevalence in HLA-C*06:02-negative persons with a consistent trend for traits like ischaemic hypertension, ischaemic heart disease, and dyslipidaemia in both datasets. However, only hypertension demonstrated statistical significance (P<0.0001 for both datasets).

In addition, clinical subtypes were evaluated according to status of positive or negative presence of HLA-C*06:02 in BSTOP. “We confirmed the previously established association of a high prevalence of guttate psoriasis and a lower prevalence of nail involvement in HLA-C*06:02-positive compared with HLA-C*06:02-negative psoriasis,” Dr Ramessur commented.

“These findings are suggestive of a different contribution of genetic effects between the sexes and highlight the importance of considering sex stratification for future genetic analyses to help identify potential sex-specific disease mechanisms,” underlined Dr Ramessur.

1. 
   
   1. Ramessur R, et al. Differences in clinical features and comorbid burden between HLA-C*06:02 carrier groups in more than 9000 people with psoriasis. FC21, Psoriasis from Gene to Clinic 2021, 9–11 December.
   2. Douroudis K, et al. J Invest Dermatol. 2021;S0022-202X(21)02473–8.
   3. Fan X, et al. Acta Derm Venereol. 2007;87(4):335–340.
   4. Dand N, et al. J Allergy Clin Immunol. 2019;143(6):2120–2130.
   5. Gudjonsson JE, et al. J Invest Dermatol. 2006;126(4):740–745.

 

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Posted on 2 February, 2022