Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
AGTRL1 and PRKCH Are Genetic Risk Factors for Antiphospholipid Syndrome.
Koike2, Takao, Atumi2, Tatsuya, Yasuda2, Shinsuke, Nakagawa2, Yasuko, Otomo2, Kotaro, Kato2, Masaru, Fujieda2, Yuichiro
Single nucleotide polymorphisms (SNPs) of Angiotensin receptor-like1 (AGTRL1) and Protein kinase C eta (PRKCH) were reported to be associated with cerebral infarction in recent genomewide association study in Japanese population. AGTRL1, also named APJ, is a member of the G protein-coupled receptor gene family and has important roles for the modulation of angiogenesis and also act as a human immunodeficiency virus coreceptor. PRKCH regulates various important cellular functions including proliferation, differentiation and apoptosisis is mainly expressed in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions. In this study, we investigated the possible association of the functional SNP in an Sp1-binding site of AGTRL1 gene (rs9943582, G/A) and the nonsynonymous SNP (rs223050, G/A, Val372Ile) in PRKCH gene with antiphospholipid syndrome (APS) in Japanese population.
Patients and Methods:
Genomic DNA samples were obtained from 111 patients with APS (45 primary APS and 66 secondly APS), 296 patients with systemic lupus erythematosus (SLE) in the absence of APS and 428 healthy controls. Among APS group, seventy nine patients (71%) had arterial or thrombosis, 58 (52%) arterial thrombosis, 37 (33%) venous thrombosis and 52 (47%) cerebral infarction, respectively. AGTRL1 SNP (rs9943582) was genotyped using TaqMan SNP genotyping assay and PRKCH SNP (rs2230500) was genotyped using direct sequencing. Chi-square tests and Odds ratio were used for statistical analysis after evaluation for Hardy-Weinberg equilibrium. In addition, the stratification analysis by thrombotic events was performed.
Both AGTRL1 rs9943582 G allele and PRKCH rs2230500 A allele frequencies were significantly increased in patients with APS (OR=1.43, 95%Cl:1.032.31 and OR=1.89, 95%Cl: 1.173.05, respectively). No association was found between these 2 SNPs and SLE in the absence of APS. In the stratification analysis by clinical manifestations of APS, both AGTRL1 and PRKCH alleles were associated with arterial or venous thrombotic events in patients with APS (OR=1.69, 95%Cl:1.152.49 and OR=1.58, 95%Cl: 1.042.38, respectively)
The functional SNP in an Sp1-binding site of AGTRL1 gene (rs9943582, G/A) and the nonsynonymous SNP (rs223050, G/A, Val372Ile) in PRKCH are associated with APS and thrombotic events in patients with APS. Our results suggest that these 2 SNPs are additional genetic risk factors for APS, especially thrombotic events in APS in Japanese population.
To cite this abstract, please use the following information:
Koike, Takao, Atumi, Tatsuya, Yasuda, Shinsuke, Nakagawa, Yasuko, Otomo, Kotaro, Kato, Masaru, et al; AGTRL1 and PRKCH Are Genetic Risk Factors for Antiphospholipid Syndrome. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2