RALEIGH, N.C. – Psoriasis patients who possess the HLA-Cw6 allele appear to be protected against the increased risk of cardiovascular and metabolic comorbidities associated with the disease.
In a study that included 199 psoriasis patients under the age of 40, those who carried the histocompatibility antigen HLA-Cw6 allele had a 66% reduction in the prevalence of comorbid hypertension and a 72% reduction in dyslipidemia, compared with HLA-Cw6-negative psoriasis patients, according to Dr. Trilokraj Tejasvi of the University of Michigan, Ann Arbor.
This is a particularly intriguing finding, he noted, because previous studies have demonstrated that HLA-Cw6-positive psoriasis patients tend to have more severe skin disease, an earlier age at disease onset, higher rates of the guttate and eruptive forms of psoriasis as well as Koebner phenomenon, and more extensive disease (J. Invest. Dermatol. 2002;118:362-5).
Moreover, other studies have shown that patients with more severe psoriasis tend to have higher rates of comorbid cardiovascular and metabolic disorders. For example, a large recent study that included 4,065 psoriasis patients aged 45-65 years and nearly 41,000 age- and physician practice-matched controls showed that the risk of comorbid metabolic syndrome increased from 1.2-fold in patients with mild psoriasis to twofold in those with severe psoriasis, compared with controls (J. Invest. Dermatol. 2012;132:556-62).
A strikingly similar twofold increased risk of the metabolic syndrome in psoriasis patients was recently reported based upon data from the National Health and Nutrition Examination Survey for 2003-2006 (Arch. Dermatol. 2011;147:419-24).
Since neither the NHANES psoriasis patients nor those in the U.K. study underwent genotyping, there is no way of knowing what proportion of those who were HLA-Cw6-positive had the metabolic syndrome, Dr. Tejasvi noted.
In a recent, still-to-be-published genome-wide association study, he and his colleagues found that all known psoriasis-associated single nucleotide polymorphisms explained roughly 22% of the disease’s heritability – and nearly half of were because of genes located at HLA-C.
The study included 1,134 psoriasis patients and 1,174 unaffected controls who underwent genomic DNA analysis. He and his coinvestigators examined the rates of hypertension, dyslipidemia, acute MI, and diabetes mellitus in the two groups.
One analysis was restricted to the 199 psoriasis patients and 392 controls under age 40, since the comorbid conditions under scrutiny tend to less frequently in younger people. In this under-40 analysis, the prevalence of diabetes wasn’t significantly different between psoriasis patients and controls. Neither was a history of MI.
However, 15% of the younger psoriasis patients carried the diagnosis of hypertension, compared with 6.8% of controls, and 29% of the psoriasis patients were dyslipidemic, compared with 10.5% of controls. Thus, psoriasis patients under age 40 were 2.2-fold more likely than controls to be hypertensive and 2.75-fold more likely to be dyslipidemic. Both differences were highly significant.
The prevalence of hypertension among 80 HLA-Cw6-positive psoriasis patients under age 40 was 7.5%, compared with 22% in HLA-Cw6-negative psoriasis patients under age 40. And the prevalence of dyslipidemia in the HLA-Cw6-positive group was 12.5% vs. 44% in the HLA-Cw6-negative psoriasis patients.
The under-40 psoriatic HLA-Cw6 carriers and noncarriers were essentially the same in terms of body mass index – a mean of 28 kg/m2 in both groups – and in mean age at evaluation, which was 28 years in the HLa-Cw6-positive patients and 29 years in the HLA-Cw6-negative cohort, Dr. Tejasvi reported.
Several key findings stood out in the analysis of the overall study population comprised of 1,134 psoriasis patients and 1,174 controls. One was that among control patients without psoriasis, HLA-Cw6 status was unrelated to comorbid hypertension, dyslipidemia, diabetes, or a positive history for MI. And in the full group of psoriasis patients, hypertension and dyslipidemia remained significantly less common among those who were HLA-Cw6-negative, although the association was less robust than in the below-40 subgroup. Specifically, HLA-Cw6 carriers with psoriasis were 24% less likely to be hypertensive and 25% less likely to have dyslipidemia than psoriatic HLAL-Cw6 noncarriers.
Dr. Tejasvi commented that an HLA-Cw6 protective effect against hypertension and dyslipidemia isn’t the only possible explanation for the lower rates of these two components of the metabolic syndrome found in HLA-Cw6-positive psoriasis patients. The alternate possibility is that HLA-Cw6 noncarrier status in psoriasis patients is associated with other genetic loci that increase the risk of dyslipidemia and hypertension. Sorting this out will require a prospective study with a large sample size.
The study was sponsored by the National Institutes of Health. Dr. Tejasvi reported having no financial conflicts.