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Association of factor V gene polymorphism with arteriovenous graft failure.

ABSTRACT: Dialysis grafts fail due to recurrent stenosis and thrombosis. Vasoactive and prothrombotic substances affecting intimal hyperplasia or thrombosis may modify graft outcomes.Genetic polymorphisms association study of patients enrolled in a multicenter randomized clinical trial.354 Dialysis Access Consortium (DAC) Study patients receiving a new graft with DNA samples obtained. Participants were randomly assigned to treatment with aspirin plus dipyridamole versus placebo.DNA sequence polymorphisms for the following candidate genes and their interaction with the study intervention: methylenetetrahydrofolate reductase (MTHFR), heme oxygenase 1 (HO-1), factor V (F5), transforming growth factor ?1 (TGF?1), klotho, nitric oxide synthase (NOS), and angiotensin-converting enzyme (ACE).Graft failure (>50% stenosis, angioplasty, thrombosis, surgical intervention, or permanent loss of function).During a median patient follow-up of 34.3 months, 304 grafts failed. After adjusting for clinical factors (patient age, sex, access location, diabetes, cardiovascular disease, baseline aspirin use, body mass index, timing of graft placement, and study treatment) and genetic ancestral background, single-nucleotide polymorphism rs6019 of the factor V gene was associated significantly with graft failure in a dominant model (HR of 1.70 [95% CI, 1.32-2.19; P < 0.001] for G/C and G/G genotypes vs C/C genotypes). There was no significant association between graft failure and polymorphisms of MTHFR, HO-1, TGF?1, klotho, NOS, or ACE.Small sample size.The rs6019 genotype of Factor V is associated with increased risk of graft failure. Anticoagulation may reduce graft failure in patients with the G/C or G/G genotypes.

SUBMITTER: Allon M

PROVIDER: S-EPMC3328616 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Association of factor V gene polymorphism with arteriovenous graft failure.

Allon Michael M Zhang Li L Maya Ivan D ID Bray Molly S MS Fernandez Jose R JR

American journal of kidney diseases : the official journal of the National Kidney Foundation 20120124 5

<h4>Background</h4>Dialysis grafts fail due to recurrent stenosis and thrombosis. Vasoactive and prothrombotic substances affecting intimal hyperplasia or thrombosis may modify graft outcomes.<h4>Study design</h4>Genetic polymorphisms association study of patients enrolled in a multicenter randomized clinical trial.<h4>Setting & participants</h4>354 Dialysis Access Consortium (DAC) Study patients receiving a new graft with DNA samples obtained. Participants were randomly assigned to treatment wi ...[more]

PMID: 22281051

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Project description:Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The ?2 test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 (G?C) of TCF21 is a susceptibility locus for hypertension.

Project description:ImportanceInitial hemodialysis access with arteriovenous fistula (AVF) is associated with superior clinical outcomes compared with arteriovenous graft (AVG) and should be the procedure of choice whenever possible. To address the national underuse of AVF in the United States, the Centers for Medicare & Medicaid has established an AVF goal of 66% or greater in 2009.ObjectiveTo explore contemporary practice patterns and physician characteristics associated with high AVG use compared with AVF use.Design, setting, and participantsThis review of 100% Medicare Carrier claims between January 1, 2016, and December 31, 2017, includes both inpatient and outpatient Medicare claims data. All patients undergoing initial permanent hemodialysis access placement with an AVF or AVG were included. All surgeons performing more than 10 hemodialysis access procedures during the study period were analyzed.ExposuresPlacement of an AVF or AVG for initial permanent hemodialysis access.Main outcomes and measuresA surgeon-level AVG (vs AVF) use rate was calculated for all included surgeons. Hierarchical logistic regression modeling was used to identify patient-level and surgeon-level factors associated with AVG use.ResultsA total of 85 320 patients (median age, 70 [range, 18-103] years; 47 370 men [55.5%]) underwent first-time hemodialysis access placement, of whom 66 489 (77.9%) had an AVF and 18 831 (22.1%) had an AVG. Among the 2397 surgeons who performed more than 10 procedures per year, the median surgeon level AVG use rate was 18.2% (range, 0.0%-96.4%). However, 498 surgeons (20.8%) had an AVG use rate greater than 34%. After accounting for patient characteristics, surgeon factors that were independently associated with AVG use included more than 30 years of clinical practice (vs 21-30 years; odds ratio, 0.85 [95% CI, 0.75-0.96]), metropolitan setting (odds ratio, 1.25 [95% CI, 1.02-1.54]), and vascular surgery specialty (vs general surgery; odds ratio, 0.77 [95% CI, 0.69-0.86]). Surgeons in the Northeast region had the lowest rate of AVG use (vs the South; odds ratio, 0.83 [95% CI, 0.73-0.96]). First-time hemodialysis access benchmarking reports for individual surgeons were created for potential distribution.Conclusions and relevanceIn this study, one-fifth of surgeons had an AVG use rate above the recommended best practices guideline of 34%. Although some of these differences may be explained by patient referral practices, sharing benchmarked performance data with surgeons could be an actionable step in achieving more high-value care in hemodialysis access surgery.

Dataset Information

Association of factor V gene polymorphism with arteriovenous graft failure.

Publications

Association of factor V gene polymorphism with arteriovenous graft failure.

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