The Phenotyping and Genotyping of Taiwanese Patients With Obstructive Sleep Apnea
The Phenotyping and Genotyping of Taiwanese Patients With Obstructive Sleep Apnea
The growing evidence showed that the OSA is a heritable complex genetic disease where the
 genetic basis contributed the development of OSA and its sequel. The phenotyping of OSA
 include high level and intermediate level. The former indicates the AHI, and later includes
 craniofacial morphology, ventilator control, obesity, and sleepiness vulnerability.

 Many studies tried to determine the association of candidate genes with OSA through
 association studies. However, the results were conflicting. We identified 37 candidate genes
 involved in six biologic pathways of OSA reported in previous literatures, including
 oxidative phosphorylation, cell signaling, apoptosis, cellular adhesion and motility, cell
 cycle, and cytokine/chemokine.

 To investigate the association between phenotype and genotype of OSA, we conducted this
 cross-sectional study by recruiting the patients of moderate-severe OSA (index proband) and
 their first and second-degree family members, and friends and their family members (control
 family) and using candidate genes reported in the literature and whole genome SNP array for
 genotype approach.
Obstructive sleep apnea (OSA) is characterized with recurrent collapse of upper airway during
 sleep resulting in hypoxia and sleep fragmentation. Patients of OSA might have symptoms like
 snoring, non-restorative sleep, witnessed apnea, and excessive daytime sleepiness. Currently,
 polysomnography is the gold standard for diagnosing OSA and the apnea-hypopnea index (AHI) is
 the parameters to indicate the severity of OSA. However, AHI poorly correlated with clinical
 severity of OSA, where the symptoms of patients with the identical AHI could vary from
 minimal to striking. The sequels of OSA include cardiovascular diseases, metabolic disorders,
 and neurocognitive dysfunctions. Till now, continuous positive airway pressure (CPAP) is the
 standard treatment for OSA where it can effectively improve daytime sleepiness, blood
 pressure, metabolic abnormalities, and quality of life, especially in patients with daytime
 sleepiness.

 The growing evidence showed that the OSA is a heritable complex genetic disease where the
 genetic basis contributed the development of OSA and its sequel. The phenotyping of OSA
 include high level and intermediate level. The former indicates the AHI, and later includes
 craniofacial morphology, ventilator control, obesity, and sleepiness vulnerability. Many
 studies tried to determine the association of candidate genes with OSA through association
 studies. However, the results were conflicting. To clarify the influence of genotyping on
 phenotyping, we reported a Chinese family with congenital central hypoventilation syndrome
 (CCHS) that had a clinical spectrum ranging from newborn fatality to adulthood. Genetic
 analysis was used to confirm the presence of the PHOX2B expansion mutation. Moreover, to
 clarify the association between ACE I/D polymorphisms and OSA, we undertook a meta-analysis
 on all studies published in this area. It has not demonstrated an association between the ACE
 I/D polymorphism and OSA susceptibility irrespective of ethnicity, population sample or the
 presence/absence of co-morbid hypertension.

 Nowadays, a couple of studies tried to genome-wide profiled the candidate genes involved in
 the biologic pathway of OSA. The whole genome scan identified chromosomes 2p 及19p and
 chromosomes 8q was associated with AHI in Caucasian and African American, respectively, which
 is independent of BMI. Also, the whole genome SNP array identified candidate genes associated
 with OSA as C-reactive protein (C-RP) and glial cell line-derived neurotrophic factor (GDNF)
 in European Americans and rs9526240 within serotonin receptor 2a (HTR2A) in African
 Americans. We identified 37 candidate genes involved in six biologic pathways of OSA
 including oxidative phosphorylation, cell signaling, apoptosis, cellular adhesion and
 motility, cell cycle, and cytokine/chemokine. Furthermore, three models were constructed to
 predict the sequel and response to 4-week and 12-week CPAP treatment, respectively.

 Since the presentations of OSA are different among races, hence database of Taiwanese
 patients with OSA is urgently needed to clarify molecular mechanisms. Through recruiting the
 patients of moderate-severe OSA (index proband) and their first and second-degree family
 members, and friends and their family members (control family) and via candidate genes
 reported in the literature and whole genome SNP array, this project aims to achieves
 following goals (1) Investigating the phenotyping and familial aggregation of OSA (2)
 Investigating the association of genotyping on phenotyping of OSA (3) Investigating the
 candidate genes and the involved biologic pathways of OSA. The anticipated contributions of
 the results include (1) Highlighting the promise of patient-tailored management (2)
 Establishing an invaluable database of phenotyping and genotyping of OSA for future research
 (3) Promoting production of biotechnology patent and business.
Inclusion Criteria:

 -  all participants needing age > 20 y/o

 -  Index proband: OSA diagnosed by overnight polysomnography (AHI>30 or AHI>15 needing
 therapeutic intervention)

 -  Index family: first-degree, second-degree relatives, or spouse of index proband

 -  Control proband: friends recommended by index proband, who lived in the same
 environment as index proband

 -  Control family: first-degree, second-degree relatives, or spouse of control proband

 Exclusion Criteria:

 -  Severe CHF, COPD, CKD

 -  Psychiatric disorder who can't coordinate to receive evaluation

 -  Autoimmune disorders

 -  Other sleep disorders

 -  Refusing to anticipate or involving other study at the same time