Genetic polymorphisms of hypoxia-inducible factor-1 alpha and cardiovascular disease in hemodialysis patients.
BACKGROUND
Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis patients.


METHODS
Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1alpha were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed.


RESULTS
A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5' upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03-0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12-0.72).


CONCLUSIONS
Genetic polymorphisms of HIF-1alpha were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.
Zheng
Zhen Lon
ZL
Department of Internal Medicine, Gachon University of Medicine and Science, Incheon, Korea.
Hwang
Young-Hwan
YH
Kim
Seong Kyun
SK
Kim
Sejoong
S
Son
Min Jung
MJ
Ro
Han
H
Sung
Su-Ah
SA
Lee
Hyun Hee
HH
Chung
Woo Kyung
WK
Joo
Kwon Wook
KW
Yang
Jaeseok
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000534:rehabilitation*; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006435:Renal Dialysis / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D055815:Young Adult
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit