Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA-C$\ast$06 Status

Abstract

The human leukocyte antigen-C ∗ 06 (HLA-C ∗ 06, formerly HLA-Cw6) is the main genetic biomarker in psoriatic disease. It has been related to several phenotypic traits in psoriatic disease, but its role in relation to cardiometabolic comorbidities is unknown at present. Here, we analyze the potential connections between this biomarker and the cardiometabolic profile of these patients. We carried out a cross-sectional observational study including 400 patients recruited at a single university hospital. Clinical and classical cardiometabolic factors were compared between HLA-C ∗ 06-positive and HLA-C ∗ 06-negative individuals (OR with 95% CI). Multivariate regression analyses were carried out to check for disease traits associated with different cardiometabolic risk factors. The study population included 215 men (53.8%) and 185 women (46.2%), mean age of 46 ± 15 years , and an average disease evolution of 17 ± 12.6 years . Ninety-three (23.3%) patients met CASPAR criteria for psoriatic arthritis. HLA-C ∗ 06 carriers ( n : 160, 40%) showed an earlier age at disease onset, psoriasis family history, and more severe skin disease (type I disease). After correcting for age, sex, and disease duration, they also showed less hypertension (13.8% vs. 24.2%, OR 0.7 (95% CI: 0.42-0.78), p = 0.025 ), lower waist circumference ( 94.4 ± 13.7 vs. 98.3 ± 13.8 cm ), and lower BMI ( 27 ± 4.4 vs. 28.1 ± 4.8 , p < 0.05 ). We confirmed the well-known association between HLA-C ∗ 06 and type I psoriatic disease. As a novel finding, patients carrying HLA-C ∗ 06 showed a better cardiometabolic profile. In any case, these findings need further confirmation.

A partitioned polygenic risk score reveals distinct contributions to psoriasis clinical phenotypes across a multi-racial cohort

“…Many studies on psoriasis cardiometabolic comorbidities have focused mainly on its relationship with the HLA-C*06:02 allele. HLA-C*06:02-positive status is often associated with lower central adiposity, lower incidence of hypertension, and a lower prevalence of other cardiometabolic comorbidities (30,34,35). These are all consistent with our HLA-C*06:02 results which were found to be protective against high blood pressure and high cholesterol.…”

Influence of the HLA-Cw6 Allele and IFIH1/MDA5 Gene Variants on the Cardiometabolic Risk Profile of Patients with Psoriatic Disease

“…In a previous study by our group, we had detected a cardiometabolic endotype linked to HLA-Cw6 [4]. However, that study was carried out for clinical phenotyping purposes (in fact, the characterization of the PsA population was much finer), while the present cohort was constructed for genotyping studies, so the collection of variables was much more selective and exhaustive (for example, in the first cohort no information on fatty liver disease was collected, while in the cohort of the present study it was).…”

“…In fact, at least two recent independent studies carried out in populations of European Caucasian ancestry have found associations between HLA-Cw6 and a smaller waist circumference, less visceral adiposity, and, in general, a "protective" tendency against the development of certain CV risk factors such as hypertension. Thus, in these studies, the reduction in the risk of hypertension conferred by HLA-Cw6 has been around 30% [4,5]. A study carried out in a Spanish population also found a reducing effect of HLA-Cw6 on the risk of liver fibrosis in subjects with PsA, while curiously enough, the presence of hypertension increased this risk [7].…”

“…There are also repeated reports regarding the relationship between this allele and a better response to certain therapies [3,10], as well as links with other characteristics of psoriatic disease, such as the negative relationship with nail dystrophy [3,5], also found in our study (OR 0.40, p < 0.001). Although the connection between HLA-Cw6 and a lower presence of diabetes [11] is known, it has not been until very recent times (the last two years) that studies have started to appear that connect this allele with a better overall cardiometabolic risk profile [4][5][6]. In fact, at least two recent independent studies carried out in populations of European Caucasian ancestry have found associations between HLA-Cw6 and a smaller waist circumference, less visceral adiposity, and, in general, a "protective" tendency against the development of certain CV risk factors such as hypertension.…”

“…In addition to being associated with severe, early onset, familial psoriasis (type I disease), HLA-Cw6 has been associated with longer psoriasis-arthritis latency, a better response to certain therapies (ustekinumab and methotrexate), and, very recently, to a better cardiometabolic risk profile [4][5][6]. In this last sense, two independent groups of researchers have related the positivity of this biomarker to a lower risk of hypertension and less visceral adiposity [4,5]. Also, very recently, Spanish researchers have found a link between HLA-Cw6 and a lower risk of liver fibrosis in PsA [7].…”