Polymorphism in the promoter region of the klotho gene (G-395A) is associated with early dysfunction in vascular access in hemodialysis patients.
OBJECTIVE
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.
Kim
Youngsu
Y
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
Jeong
Sun Joo
SJ
Lee
Hyung Suk
HS
Kim
Eun Jung
EJ
Song
Young Rim
YR
Kim
Sung Gyun
SG
Oh
Ji Eun
JE
Lee
Young Ki
YK
Seo
Jang Won
JW
Yoon
Jong Woo
JW
Koo
Ja Ryong
JR
Kim
Hyung Jik
HJ
Noh
Jung Woo
JW
Park
Seung Ho
SH
D000368:Aged; D001166:Arteriovenous Shunt, Surgical; D002408:Catheters, Indwelling; D015331:Cohort Studies; D005260:Female; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics* / Q000628:therapy; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D006435:Renal Dialysis; D014652:Vascular Diseases / Q000150:complications / Q000235:genetics; D014654:Vascular Patency / Q000235:genetics*
D005966:Glucuronidase; D000090265:Klotho Proteins