Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Methods: We studied two independent cohorts of primary APS patients of European descent, consisting of 89 patients and 3072 healthy controls from Spain, and 133 patients and 1560 healthy controls from Italy. Genotyping of ~200,000 variants was performed using the HumanImmuno v1 BeadChip. Genetic association analysis was performed following rigorous quality control measures. A meta-analysis between the two cohorts was performed to identify susceptibility loci for primary APS. Additional genetic variants within loci of suggestive genetic association were imputed up to the 1000 Genomes Project density and then included in the analysis.
Results: We identified a novel genetic susceptibility locus for primary APS in PLEK, encoding pleckstrin, which plays an important role in hemostasis and platelet function (odds ratio= 1.71, P=7.89 x 10-6). Importantly, expression quantitative trait loci (eQTL) analysis revealed that the disease risk allele in PLEK is associated with significant reduction in PLEK mRNA expression (P=2.6 x 10-6), and is located within an active enhancer region identified by histone H3K27 acetylation and DNase hypersensitivity. Our data also confirmed the genetic association between APS and STAT4 (odds ratio= 1.66, P=4.67 x 10-6). The association within the HLA was the most significant genetic association detected for APS in our study, with the most robust effect within HLA class II upstream of HLA-DQA1 (OR 1.87, P=2.45 x 10-8).
Conclusion: This is the first genome-wide association study in primary APS. Our findings suggest a novel putative functional genetic susceptibility locus for primary APS in PLEK, and identify genetic susceptibility loci within the HLA class II locus and the common autoimmunity locus in STAT4. *MAR and AS equally contributed to this work
To cite this abstract in AMA style:Gensterblum E, Hughes T, Martínez-Bueno M, Borghi MO, Pons-Estel GJ, Espinosa G, Zhernakova A, Wijmenga C, Cervera R, Meroni PL, Alarcón-Riquelme M, Sawalha A. Identification of Novel Genetic Susceptibility Loci in Primary Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/identification-of-novel-genetic-susceptibility-loci-in-primary-antiphospholipid-syndrome/. Accessed December 5, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-novel-genetic-susceptibility-loci-in-primary-antiphospholipid-syndrome/