BACKGROUND/AIMS: Vascular access dysfunction is an important cause of morbidity and mortality in hemodialysis (HD) patients. Recent studies have shown that a klotho gene mutation is related to endothelial dysfunction, thrombosis, and arteriosclerosis, which are regarded as causes of vascular access dysfunction. We investigated the relationship between the klotho G-395A polymorphism and early dysfunction in vascular access in HD patients. METHODS: Patients who underwent vascular access operations between 1999 and 2002 were enrolled (n=126). Genotyping was performed by allelic discrimination using a 5'-nuclease polymerase chain reaction assay. Clinical data that could be relevant to access dysfunction were obtained from medical records. Early dysfunction of vascular access was defined as the need for any angioplastic or surgical intervention to correct or replace a poorly or nonfunctioning vascular access within 1 year and at least 8 weeks after initial access placement. RESULTS: Of the 126 patients, the genotype frequency of G-395A was 72.2% for GG (n=91), 24.6% for GA (n=31), and 3.2% for AA (n=4), and the frequency of minor allele was 0.155. Clinical data were similar between the two groups, divided according to the status of the A allele. Early dysfunction occurred in 34 (27.0%) of patients, but it occurred at a significantly higher rate in A allele carriers (45.7%, 16/35) than in noncarriers (19.8%, 18/91; p=0.003). CONCLUSIONS: Our results suggest that the klotho G-395A polymorphism could be a risk factor for early dysfunction of vascular access in HD patients.
Aged ; *Arteriovenous Shunt, Surgical ; Catheters, Indwelling ; Cohort Studies ; Female ; Glucuronidase/*genetics ; Humans ; Kidney Failure, Chronic/complications/*genetics/therapy ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Promoter Regions, Genetic/genetics ; *Renal Dialysis ; Vascular Diseases/complications/genetics ; Vascular Patency/*genetics

BACKGROUND/AIMS: Chronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients. METHODS: A total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay. RESULTS: The GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population. CONCLUSIONS: The IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.
Adult ; Aged ; Arteriovenous Shunt, Surgical/*adverse effects ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; Chi-Square Distribution ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Frequency ; Genotype ; Graft Occlusion, Vascular/blood/ethnology/*genetics/physiopathology ; Humans ; Interleukin-6/blood/*genetics ; Kidney Failure, Chronic/blood/ethnology/genetics/immunology/*therapy ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Phenotype ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Promoter Regions, Genetic ; *Renal Dialysis ; Republic of Korea ; Time Factors ; Treatment Outcome ; Vascular Patency/*genetics