An association study exploring the genetic relationship of psoriatic arthritis and obesity

Abstract

Objective: To determine if there is a genetic component causing psoriatic arthritis (PsA) patients to have higher BMIs when compared to the general population. Method: 696 obese samples were identified from a previous genetic study on obesity which were genotyped using a PsA SNP panel. 650 PsA patients who were examined for PsA related anthropometric measures were genotyped using an obesity SNP panel. An obesity panel was created using a gene prioritization method to create a 46 SNP obesity-weighted panel. Two separate quantitative trait analyses were performed to obtain the association between BMI and genotype of the subsequent panels using a linear regression model. Bonferroni correction was used to adjust for multiple comparisons. Results: Genotypes of two PsA-weighted SNPs, rs10782001 (FBXL19) and rs3131382 (HLA-B39), showed a significant difference with BMI. Patients with the FBXL19 variant had an average BMI in the presence of GG genotype of 37.2 kg/m² vs 34.3 kg/m² for the AA genotype (p=0.0007). Patients with the HLA-B39:05 variant had an average BMI with the TT genotype of 47.1 kg/m2 vs 35.4 kg/m² for the CC genotype (p=0.00005). One obesity-weighted SNP, rs11915371 (SAMMSON/FOXP1), showed a significant difference of BMI between genotypes in PsA patients. The average BMI of those with the CC genotype was 32.42 kg/m² compared to an average BMI of 29.77 kg/m² with the TT genotype (p=0.0009). Conclusion: Homozygotes for the minor allele of SNPs within HLA-B*39, FBXL19, and SAMMSON/FOXP1 have shown to have an increased BMI, suggesting a potential genetic link between these genes and PsA and obesity.