title: A pilot study of genetic polymorphisms and hemodialysis vascular access thrombosis.
abstract: Vascular access thrombosis (VAT) remains a significant problem worldwide. This study determined the association between VAT and 7 candidate gene polymorphisms (factor V Leiden 1691G>A, factor II 20210G>A, methylenetetrahydrofolate reductase 677C>T, angiotensin converting enzyme 287 base pair (bp) insertion/deletion, transforming growth factor-beta1 869T>C and 915G>C, NOS3 -786T>C and intron 4 27 bp tandem repeat, and endotoxin receptor CD14 -159C>T). This was a retrospective case-control pilot study conducted in 101 hemodialysis patients at a large tertiary-care, University health-science center. Sixty cases that experienced frequent VAT and 41 controls that had not experienced VAT in at least 3 years were evaluated for demographics and genotyping. These data were summarized, and univariable and multivariable regression models were constructed. Univariate VAT predictors included the NOS3 420 bp allele (P=0.03) and the presence of a central venous dialysis catheter (P<0.01). Aspirin use was protective against VAT (P=0.02). In the multivariate analysis, the dialysis access type remained a significant predictor of thrombosis (P<0.01), while aspirin use retained its protective status (P=0.01). Statin use was associated with the cases (P=0.02); however, the NOS3 420 bp allele failed to improve the model. These data confirm that central venous dialysis catheter access is associated with thrombosis, while aspirin use appears protective. The NOS3 420 bp allele may have an association with thrombosis; however, further epidemiologic data evaluating large dialysis registries are needed to confirm our observation.
authors.affiliation: Department of Pharmacy, Virginia Commonwealth University, Richmond, 23298-0533, USA. dbrophy@vcu.edu
authors.forename: Donald F
authors.initials: DF
authors.lastname: Brophy
authors.forename: Bonny L
authors.initials: BL
authors.lastname: Bukaveckas
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferreira-Gonzalez
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Martin
authors.forename: Todd W B
authors.initials: TW
authors.lastname: Gehr
mesh_terms: D000328:Adult; D000368:Aged; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D005165:Factor V / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics; D006435:Renal Dialysis / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D053773:Transforming Growth Factor beta1; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2)