Hypoxia Inducible factor1-Alpha Genetic Polymorphism of Obstructive Sleep Apnea

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00498693
First received: July 8, 2007
Last updated: January 12, 2009
Last verified: January 2009

July 8, 2007
January 12, 2009
March 2006
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Complete list of historical versions of study NCT00498693 on ClinicalTrials.gov Archive Site
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Hypoxia Inducible factor1-Alpha Genetic Polymorphism of Obstructive Sleep Apnea
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Specific Aim

  1. To identify specific SNPs of HIF-1 gene related to cardiovascular disease in OSA patients (CVD-OSA)
  2. To assay the functional activity of high risk SNPs of HIF-1 on the transcription of VEGF gene
  3. To confirm that the serum level of VEGF in CVD-OSA patients with high risk SNPs of HIF-1 are higher than CVD-OSA patients without

Obstructive sleep apnea syndrome(OSAS) is characterized with recurrent collapse of upper airway during sleep and results in hypoxia and sleep fragmentation. The repeated episodes of hypoxia and sympathetic hyperactivity result in cardiovascular complications, including atherosclerosis, hypertension, coronary artery disease and heart failure. Our data showed among 309 consecutively-admitted OSA patients, 54% patients had cardiovascular diseases.

The hypoxia in OSA is characterized as chronic and intermittent, which leads to sophisticated adaptive mechanisms, like activations of transcriptional factors and critical signaling pathways. HIF-1 is a central component of transcriptional factors involved in hypoxia-induced transcription of specific genes. There are two subunits of HIF-1 transcription factor, which interact with the consensus hypoxia response element in the target genes. The HIF-1 alpha activity is regulated by proline hydroxylation modification and ubiquitination, which is oxygen-tension dependent. HIF-1 alpha target genes encode proteins that increase oxygen delivery, such as vascular endothelial growth factor(VEGF). Our oligo-microarray study showed both HIF and VEGF expression in OSA patients was 1.3 times of control group, which decreased to 46% and 57% respectively after one-month CPAP treatment.

HIF-1 alpha polymorphism could result in increased HIF-1 alpha activity and microvessel density. In clinical observation, HIF-1 polymorphism has been reported to be associated with high altitude adaptation, formation of coronary collaterals in CAD and phenotype of cancer. These findings were possibly explained with effect of HIF on modulation of VEGF.

Several genetic polymorphisms were reported to be associated with OSA, which included TNF alpha, angiotensin converting enzyme and haptoglobin. Only hepatoglobin phenotype is proved to be a risk factor for cardiovascular disease in OSA. In most studies, the patient number is less than suggested.

Therefore, in this study, we hypothesized that HIF-1 gene polymorphism was associated with cardiovascular disease in OSA. And by using large-scale of study population(1000 OSA patients), we examined all regions of the HIF-1 alpha to detect single-nucleotide polymorphisms(SNPs), evaluated the pattern of linkage disequilibrium to compose haplotypes in the gene, and performed association studies in OSA patients with and without cardiovascular disease to achieve the following 3 objectives:(1)To identify specific SNPs of HIF-1 alpha gene related to cardiovascular disease in OSA patients (CVD-OSA).(2)To assay the functional activity of high risk SNPs of HIF-1 alpha on the transcription of VEGF gene.(3)To confirm that the serum level of VEGF in CVD-OSA patients with high risk SNPs of HIF-1 are higher than CVD-OSA patients without. The findings are expected to stratify the risk of OSA patients to specific outcome, or response to specific therapy.

Observational
Observational Model: Case Control
Time Perspective: Prospective
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Probability Sample

patients referred sleep center to rule out obstructive sleep apnea

Sleep Apnea, Obstructive
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Pandit JJ. Structure-function relationships: a breath of fresh air--or just more hot air--in sleep apnoea research? Respiration. 2008;76(1):16-8. Epub 2008 May 8. No abstract available.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1000
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Inclusion Criteria:

  • Severe obstructive sleep apnea (AHI>=30/hr) age, sex, BMI match control subject

Exclusion Criteria:

  • Patients were excluded when: (1) refused to participate in this study, (2) had severe obstructive pulmonary disease or active neurological events, (3) enrolled in other studies at the same time
Both
18 Years and older
No
Contact: Peilin Lee, M.D. +886-2-23562905 peilin1986@yahoo.com.tw
Taiwan
 
NCT00498693
9561701013
Yes
Peilin Lee, National Taiwan University Hospital
National Taiwan University Hospital
Not Provided
Principal Investigator: Hey-Dong Wu, M.D. National Taiwan University Hospital
National Taiwan University Hospital
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP