Background/Purpose: Human Leukocyte Antigen (HLA) class I alleles and obesity are risk factors for psoriatic arthritis (PsA). We aimed to assess whether there is an interaction between HLA risk alleles for PsA and obesity in susceptibility to PsA.

Methods: The study comprised two parts: 1) a case-only design that included patients with early PsA (<2 years) from 2 PsA cohorts, 2) a case-control design in which patients with early PsA were compared to those with psoriasis alone (PsC). Body Mass Index (BMI) at the first visit was stratified to normal (<25), overweight (25≤BMI<30) and obese (≥30). HLA genotyping was performed by sequence-specific oligonucleotide probes. The following alleles that were independently associated with PsA were analyzed: HLA-B*08, B*18, B*27, B*38, B*39 and C*06. Due to low frequency and similar structure, the effect of HLA-B*08, B*18, B*39 and B*38 was assessed in conjunction (termed “combined HLA-B alleles”). The interaction between obesity and HLA alleles was assessed by comparing the distribution of the various alleles across the three BMI categories in patients with PsA using trend test (case-only design). The interaction between HLA alleles and obesity was further investigated (case-control design) by assessing a departure from multiplicative combined effect of risk using logistic regression analysis after adjusting for age and sex and by assessing a departure from additivity by calculating the attributable proportion (AP).

Results: 637 Caucasians patients were analyzed (262 PsA, 375 PsC). Obesity was more frequent in patients with PsA compared to those with PsC (p=0.005). In addition, HLA-B*27 (p=0.0001) and the combined HLA-B alleles (p=0.03) were associated with PsA vs. PsC. A differential distribution of HLA-B alleles was observed across the 3 BMI categories in patients with PsA (case-only design) suggesting an interaction. The frequency of B*27 was higher in patients with normal weight compared to those with higher BMI (p^trend=0.005). In contrast, PsA patients who carried one of the combined HLA-B alleles tended to be heavier (p^trend=0.03). Similar findings were observed in the case-control analysis (Figure 1). A multiplicative interaction was found for the combined effect of B*27 and obesity in logistic regression analysis (OR 0.1 p=0.01) as well as for the joint effect of combined HLA-B alleles and obesity (OR 2.7 p=0.03). A significant additive interaction of combined HLA-B alleles and obesity was found with the proportion of risk due to additive interaction (AP) of 0.62 (95% CI 0.38, 0.93, p=0.0001). No interaction was found between obesity and HLA-C*06 allele.

Conclusion: An interaction was found between HLA-B alleles and obesity in PsA risk thus the effect of obesity on PsA risk may depend on the presence of HLA-B alleles.