Pleiotropic effects of n-6 and n-3 fatty acid-related genetic variants on circulating hemostatic variables. Issue 168 (August 2018)

• Record Type: Journal Article
• Authors: Weng, Lu-Chen; Guan, Weihua; Steffen, Lyn M.; Pankow, James S.; Pankratz, Nathan; Chen, Ming-Huei; Cushman, Mary; Basu, Saonli; Folsom, Aaron R.; Tang, Weihong
• Is Part Of: Thrombosis research. Issue 168(2018)
• Page Start: 53
• Page End: 59
• Publication Date: 2018-08
• Subjects: AA African American -- aPTT activated partial thromboplastin time -- ARIC the Atherosclerosis Risk in Communities Study -- CHS the Cardiovascular Health Study -- DHA docosahexaenoic acid -- DPA docosapentaenoic acid -- EA European ancestry -- EPA eicosapentaenoic acid -- FHS the Framingham Heart Study -- FVII factor VII -- FVIIc factor VII coagulant activity -- FVIII factor VIII -- FVIIIc factor VIII coagulant activity -- GWAS genome-wide association studies -- LA linoleic acid -- LD linkage disequilibrium -- Ln-fibrinogen natural log transformed fibrinogen -- Ln-FVIIIc natural log transformed factor VIII coagulant activity -- Ln-VWF natural log transformed von Willebrand factor -- PUFA polyunsaturated fatty acid -- RS the Rotterdam Study -- SHBG sex hormone-binding globulin -- QC quality control -- VWF von Willebrand factor; Hemostatic variables -- Polyunsaturated fatty acids -- Single nucleotide polymorphism -- Genetic pleiotropy; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2018.05.032
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Data from epidemiological studies and clinical trials suggest an influence of dietary and circulating polyunsaturated fatty acids (PUFAs) on the hemostasis profile. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) related to plasma PUFAs levels. We aimed to investigate whether the SNPs related to plasma PUFAs levels were also associated with plasma levels of hemostatic variables. Materials and methods: We tested the associations between 9 PUFA-related SNPs and 6 hemostatic variables in 9035 European Americans (EAs) and 2702 African Americans (AAs) in the Atherosclerosis Risk in Communities (ARIC) Study. We then conducted a replication study by looking-up our novel observed associations in three published GWAS for hemostatic factors in different EA populations. Results: We observed a novel linoleic acid-related locus at the JMJD1C region associated with factor VII activity (FVIIc): rs10740118 and rs1935, Beta (p) = −1.31 (1 × 10 −3 ) and 1.37 (5 × 10 −4 ) in EAs, respectively, and − 1.24 (5 × 10 −4 ) and 1.28 (3 × 10 −4 ) in meta-analysis of EAs and AAs of ARIC. This novel association was replicated in two of three independent EA populations ( p = 0.01 and 0.03 in meta-analyses). We confirmed previously reported associations at the docosapentaenoic acid-related GCKR locus with protein C and FVIIc and at JMJD1C with fibrinogen. Adjustment for plasma PUFAs did not abolish the associations between these loci and hemostatic variables. Conclusions: Our study identified a novel association for FVIIc at JMJD1C, a histone demethylase that plays a role in DNA repair and possibly transcription regulation and RNA processing. Highlights: We identified a novel genetic association for factor VII activity at JMJD1C This association was replicated in independent populations We also replicated the association of JMJD1C gene with fibrinogen The JMJD1C gene has been reported to show pleiotropic effects on other phenotypes