The Presence of PAI-1 4G/5G and ACE DD Genotypes Increases the Risk of Early-Stage AVF Thrombosis in Hemodialysis Patients

Abstract

Background: In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Methods: Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Results: Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, b-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x 2 = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. Conclusion: PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

Multiple preoperative and intraoperative factors predict early fistula thrombosis in the Hemodialysis Fistula Maturation Study

“…Early thrombosis (ET), 4–14 which may represent the most aggressive form of primary access failure, has been reported to occur in 6.3–19.5% of fistulas, and is associated with preoperative patient factors including thrombophilic factor gene polymorphisms 15 and radial artery diameter 16 , intraoperative factors such as surgeon experience 17 , end-diastolic velocity in the proximal feeding artery after AVF construction, and absence of bruits and postoperative factors including arterial resistive index 18 and use of anticoagulants 4, 12 , as well as intraoperative 6 and postoperative 10 fistula blood flow.…”

Candidate Gene Analysis of Arteriovenous Fistula Failure in Hemodialysis Patients

“…One explanation for these observations could be that other SNPs are involved in AVF failure or that genetic susceptibility does not play an important role in the development of AVF failure. Based on other studies that also did not find an association between most candidate SNPs and AV access failure (23)(24)(25)41), it might be that local factors, such as hemodynamics and vascular damage, have a more important role in the failure of the vascular access required for hemodialysis than the genetic background.…”

“…Furthermore, we also selected SNPs that were associated with coronary restenosis (13,17,18) and vascular aneurysm formation (19,20), because underlying mechanisms of these diseases are thought to overlap. A MEDLINE search using keywords including "hemodialysis," "arteriovenous access failure," and "single nucleotide polymorphism" identified six genes previously associated with AV access failure: TNF-a (21), klotho (22), fibrinogen-b (FGB) (23), factor V (24), and matrix metallopeptidase 1 (MMP1) (25). To broaden the search to coronary restenosis and vascular aneurysm formation, the keywords "coronary restenosis," "percutaneous coronary intervention," and "aortic aneurysm" were added, identifying another 20 candidate genes.…”

Association between ABCB1 (MDR1) Gene 3435 C>T Polymorphism and Colchicine Unresponsiveness of FMF Patients

“…[7][8][9] Colchicine is used chiefly in the treatment of FMF but is also valuable in other inflammatory diseases such as Behçet's disease, gout, and recurring pericarditis with effusion. 9,10 Three proteins play pivotal roles in colchicine pharmacokinetics: the colchicine receptor, tubulin, governs the plasma elimination half-life of the drug; intestinal and hepatic CYP3A4, key to the biotransformation of colchicine; and P-gly, a cell efflux pump that regulates the tissue distribution of colchicine, as well as its excretion via the biliary tract and kidneys. Pharmacokinetic studies have been performed using a radioimmunology assay to measure blood colchicine levels.…”