Programmed Death Ligand 1 (PD-L1) Gene Variants Contribute to Autoimmune Addison’s Disease and Graves’ Disease Susceptibility

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 23; no. 11; p. 1935
• Main Authors: Mitchell, Anna L., Cordell, Heather J., Soemedi, Rachel, Owen, Kate, Skinningsrud, Beate, Wolff, Anette Bøe, Ericksen, Martina, Undlien, Dag, Husebye, Eystein, Pearce, Simon H. S.
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.11.2009; Endocrine Society
• Subjects: Translational Highlights from Jcem
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/mend.23.11.9997

ABSTRACT Context Despite much investigation, a substantial amount of the genetic susceptibility to autoimmune diseases remains unaccounted for. Recently, a single-nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has been associated with Graves’ disease (GD) in a Japanese patient cohort. Our aim was to determine whether variants in PD-L1 are also associated with autoimmune Addison’s disease (AAD) and to replicate the previous association in patients with GD from the United Kingdom. Design and Patients We analyzed eight SNPs within PD-L1 in a United Kingdom cohort of 315 AAD subjects and 316 healthy controls. We then replicated our experiment in a cohort of 342 Norwegian AAD cases and 379 controls and in 496 United Kingdom GD subjects. Results Three of the eight SNPs studied, part of a haplotype block in the PD-L1 gene, showed modest association with both AAD and GD in the United Kingdom cohort, with maximum evidence at the marker RS1411262 [United Kingdom AAD odds ratio 1.33 (5–95% confidence interval 1.02–1.73), P(genotype) = 0.028; GD odds ratio 1.36 (5–95% confidence interval 1.07–1.72), P(genotype) = 0.033]. Association with genotypes at the same three markers was confirmed in the Norwegian AAD cohort [P(genotype) = 0.011–0.020]. A recessive effect at the most associated alleles was observed in both the AAD and GD cohorts. Conclusions We confirm the role of PD-L1 variants in GD susceptibility and extend these findings to demonstrate association in two Northern European patient cohorts with AAD. PD-L1 joins the growing number of known susceptibility loci exerting modest effects in these autoimmune disorders.