OBJECTIVETo have a better understanding of genetic contributions to the development of obstructive sleep apnea hypopnea syndrome (OSAHS) by reviewing studies on its genetic basis.

DATA SOURCESA comprehensive search of the PubMed literature without restriction on the publication date was carried out using terms "obstructive sleep apnea" and "candidate genes" or "genetics".

STUDY SELECTIONArticles were selected if they were an original research paper or meta analysis of the genetic factors of OSAHS.

RESULTSFour intermediate phenotypes were described and several candidate genes that may determine the expression and severity of OSAHS were reviewed.

CONCLUSIONMultiple gene-gene interactions occurring in genes that affect obesity, craniofacial structure, ventilator control and asleep-awake pattern may influence the expression of OSAHS in a suitable environment.

Humans ; Obesity ; genetics ; Sleep Apnea, Obstructive ; genetics

Child ; Child, Preschool ; Female ; Humans ; Male ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Sleep Apnea, Obstructive ; genetics ; physiopathology

OBJECTIVETo investigate the association between interleukin (IL)-1β genetic polymorphisms and obstructive sleep apnea syndrome (OSAS).

METHODSTotally 850 individuals with hypertension were included. All of them were checked by polysomnography in the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from January to December in 2010. According to the results of polysomnography, these subjects were divided into non-OSAS group (n=225)and OSAS group (n=625). Genetic variations were sequenced and screened at loci over functional region of IL-1β gene in 96 patients with severe OSAS.The typical loci were selected for genotyping by TaqMan-polymerase chain reaction in 850 subjects.

RESULTSOne novel and 5 known variations in the IL-1β gene were identified, and then three representative mutation loci were selected for genotyping.The allele frequency distribution of rs1143633 was significantly different between the OSAS and non-OSAS groups in the total and male populations (χ(2)=9.258, P=0.002;χ(2)=5.119, P=0.024, respectively). Although the parameters of sleep apnea monitoring showed no significant difference in individuals with CC, CT, and TT genotypes of rs1143633 in total, male, and female populations (P>0.05), the median of the apnea hypopnea index of CT genotype was significantly higher than that of CC and TT in total and male populations and the mean of the lowest blood oxygen saturation increased in individuals with CC, CT, and TT genotypes of rs1143633 in total and male populations.Haplotype was no significantly associated with OSAS in total,male,and female populations(P>0.05).Logistic regression analysis showed that CT genotype of rs1143633 variation was a risk factor for OSAS in total and male populations (OR=1.574,95% CI=1.061-2.437,P=0.042;OR=1.887,95% CI=1.091- 3.265,P=0.023).

CONCLUSIONThe rs1143633 polymorphism in IL-1β gene may be associated with OSAS.

Adult ; Female ; Genetic Variation ; Genotype ; Humans ; Interleukin-1beta ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Sleep Apnea, Obstructive ; genetics

OBJECTIVEThe expression of glucocorticoid receptor (GR) expression in obstructive sleep apnea hypopnea syndrome (OSAHS) in children is currently unknown. The aim of this study was to determine the GR-alpha and GR-beta status in the adenoidal tissues in children with OSAHS.

METHODSThirty-four pediatric patients (aged 3-14 years, median 7.8 years) had sleep study with polysomnography before adenoidectomy. According to the criteria of apnea hypopnea index (AHI) > or = 5 /h or/and apnea index (AI) > or = 1/h, they were divided into OSAHS and non-OSAHS sub groups. The study was based on fluorescent quantitative PCR (FQ-RT-PCR) for the mRNA expression of GR-alpha and GR-beta in the adenoidal tissues in children.

RESULTSGR isoforms mRNA encoding for expression of both GR-alpha and GR-beta were detected in the adenoids of all children. GR-alpha mRNA level [(9.40 +/- 3.06) x 10(5) cDNA copies/microg total RNA] in the adenoidal tissues in OSAHS was lower than those in the non-OSAHS [(1.60 +/- 0.26) x 10(6) cDNA copies/microg total RNA] (F = 40.285, P < 0.001), whereas no differences found for GR-beta [(1.57 +/- 0.35) x 10(4) cDNA copies/microg total RNA, (1.52 +/- 0.18) x 10(4) cDNA copies/microg total RNA]. GR-alpha/GR-beta ratio was 62.3 +/- 20. 3 in OSAHS and 107.4 +/- 24.4 in non-OSAHS. AHI or AI was not related to the mRNA levels of GR-alpha and GR-beta in OSAHS or non-OSAHS.

CONCLUSIONSGR-alpha and GR-beta were detectable in the adenoidal tissues in children. These data indicated that the relationship between the expressions of GR and the clinical significance in OSAHS need further and profound investigation.

Adenoids ; metabolism ; Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; RNA, Messenger ; genetics ; Receptors, Glucocorticoid ; metabolism ; Sleep Apnea, Obstructive ; metabolism

BACKGROUNDObstructive sleep apnea hypopnea syndrome (OSAHS) is regarded as a disease with strong genetic background and associated with hypoadiponectinemia. It is worthwhile to investigate the possible correlation between the single nucleotide polymorphisms (SNPs) in the adiponectin gene and OSAHS.

METHODSWith the TaqMan polymerase chain reaction (PCR) method, the SNPs at positions 45 and 276 in the adiponectin gene were determined in Chinese of Han nationality in Nanjing district consisting of 103 OSAHS patients (OSAHS group) and 67 normal controls (control group). The association of adiponectin genotype polymorphisms at positions 45 and 276 with OSAHS was analyzed.

RESULTSNo evidence of a direct association was found between OSAHS and adiponectin genotype SNP at positions 45 and 276 (P > 0.05). However, compared with those OSAHS patients having G/T + T/T genotype at position 276, the OSAHS patients with G/G genotype showed a longer neck circumference, a prolonged duration of the longest apnea event, and an elevated level of blood cholesterol and low-density lipoprotein cholesterol (P < 0.05).

CONCLUSIONSNo direct association was suggested between OSAHS and adiponectin genotype distribution at positions 45 and 276 in Chinese of Han nationality in Nanjing district. However, in OSAHS patients, those with adiponectin G/G genotype at position 276, seemed to have a higher potential risk in development of OSAHS than those having adiponectin SNP276 G/T + T/T genotype.

Adiponectin ; genetics ; Adult ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Sleep Apnea, Obstructive ; genetics

OBJECTIVETo investigate the relationship between genetic polymorphisms of glucose transporter 4 (GLUT4) and hypoxia caused by obstructive sleep apnea syndrome (OSAS) as well as with related inflammatory factors.

METHODSConsecutive hypertension patients diagnosed at the People's Hospital of Xinjiang Uygur Autonomous Region were selected from January to December 2010. A total of 859 subjects with possible OSAS base on their histories and physical examination findings udner went the polysomnography and inflammatory factor determination, of whom 616 (72%) were diagnosed with moderate and severe hypoxia with OSAS (case group) and 243 (28%) without hypoxia or OASA (control group). Ninty-six patients from the case group underwent DNA sequencing at the functional domain of GLUT4 gene to screen for representative mutations. TaqMan PCR was used to genotyping then analyzed the relationship between locis of GLUT4 and hypoxia.

RESULTSGLUT4 genome sequencing was performed in 96 severe OSAS patients and 4 mutated sites were found, among which 3 mutated sites (rs5415, rs4517, and rs5435) were selected according to the principle of linkage disequilibrium (r² > 0.8) and minimum gene allele frequency > 5%. All of single nucleotide polymorphisms (SNP) satisfied Hardy-Weinberg equilibrium (P>0.05). A significant association of GLUT4 SNP rs5417 allele carried in control subjects, compared with moderate and severe hypoxia in OSAS patients (P<0.05); AA+AC genotype relative to CC with low oxygen levels in subjects significantly reduced. The difference existed in overweight and obese patients, as well as in those aged more than 50 years (P<0.05). AA was still an independent protective factor for hypoxia caused by OSAS (OR=0.385, 95%CI = 0.210-0.704, P=0.002). Male (OR=1.635, 95% CI=1.037-2.577, P=0.034) and total cholesterol (OR=1.600, 95% CI=1.287-1.987, P<0.001) were independent risk factors associated with hypoxia. Normal weight(OR=0.059, 95% CI=0.037-0.094, P<0.001) and high density lipoprotein cholesterol (OR=0.337, 95% CI=0.171-0.666, P=0.002)were independent protective factors for hypoxia. The levels of monocyte chemoattractant protein-1 and C-reaction protein above CC were significantly higher than AA+AC (P<0.05).

CONCLUSIONHypoxia caused by OSAS is associated with GLUT4 gene SNP rs5417.

Adult ; Aged ; Female ; Glucose Transporter Type 4 ; genetics ; Humans ; Hypoxia ; etiology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sleep Apnea, Obstructive ; complications ; genetics

OBJECTIVETo reseach the correlations between cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expressions and angiogenesis in pharyngeal tissue of patients with obstructive sleep apnea hypopnea syndrome (OSAHS).

METHODSBiopsies were obtained by uvulopalatopharyngoplasty from 40 patients with mild to severe OSAHS. Control specimens of palatopharyngeal and palatoglossal arch mucosa were retreved from 6 patients with chronic tonsillitis and proved have no related disorders. HE was used to observe the changes of pharyngeal tissue, immunohistochemical staining with antibodies against COX-2, VEGF, microvessel density (MVD) (marked with CD34).

RESULTSCOX-2 and VEGF mainly expressed at pavement-epithelium and glandular epithelium of pharyngeal tissue, and stronger COX-2 and VEGF expression was found in midrange and severe OSAHS than mild and control group (P < 0.01), so as MVD. COX-2 expression was correlated positively with VEGF expression, and had significant correlation with MVD. VEGF expression had the same correlation with MVD. These three targets had considerable relation with apnea hypopnea index (AHI) and lowest O2 saturation at night.

CONCLUSIONThere was angiogenesis which had important relationship with hypoxia degree in patients of OSAHS, and COX-2 and VEGF play a crucial role in its development.

Adult ; Cyclooxygenase 2 ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; Pharynx ; blood supply ; metabolism ; Sleep Apnea, Obstructive ; metabolism ; physiopathology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. METHODS: Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. RESULTS: The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLA- DRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index>45) than in the controls (p<0.05). CONCLUSION: This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS.
Alleles ; Apnea ; Cytotoxicity Tests, Immunologic ; Diagnosis ; Exons ; Female ; Gene Frequency ; Genetics ; Histocompatibility Testing ; HLA Antigens ; HLA-A Antigens ; HLA-A11 Antigen ; HLA-B Antigens ; HLA-DRB1 Chains ; Humans ; Lymphocytes ; Male ; Obesity ; Polysomnography ; Risk Factors ; Sleep Apnea, Obstructive*

BACKGROUNDIncreased production of reactive oxygen species (ROS) is thought to play a major role in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS). The reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex is an important source of ROS. The p22phox subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. This study aimed to investigate the relationship between NADPH oxidase subunit p22phox gene polymorphism and OSAHS.

METHODSThe genotypes of p22phox polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assay in 176 unrelated subjects of the Han population in southern region of China (including 107 OSAHS subjects and 69 non-OSAHS subjects), while the plasma concentration of superoxide dismutase (SOD) was detected in the two groups, and p22phox mRNA expression in peripheral blood mononuclear cell (PBMC) was determined with reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe phagocyte NADPH oxidase subunit p22phox mRNA expression was significantly increased in the OSAHS group than that in the non-OSAHS group (P < 0.01). Compared with the non-OSAHS control group ((85.31 +/- 9.23) U/ml), the levels of SOD were lower in patients with OSAHS ((59.65 +/- 11.61) U/ml (P < 0.01). There were significant differences in genotypes distribution in p22phox polymorphism between the two groups (P = 0.02). Compared with the non-OSAHS control group, the OSAHS group had a significantly higher T allele frequency in p22phox polymorphism (P = 0.03). There were independent effects of p22phox polymorphism on body mass index (BMI), neck circumference (NC), waist-to-hip ratio (WHR) in the OSAHS group, and the carriers of the T allele of p22phox polymorphism had greater NC, WHR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and apnea-hypopnea index (AHI) (P < 0.05), but the carriers of the T allele had lower SOD (P < 0.01) and lowest SaO(2) (P = 0.04). There was no significant difference in p22phox mRNA expression between the OSAHS groups with or without T allele (P = 0.45).

CONCLUSIONSThe NADPH oxidase subunit p22phox gene polymorphism may be associated with susceptibility to OSAHS, and it may be an important candidate gene for OSAHS.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; Body Mass Index ; China ; epidemiology ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; NADPH Oxidases ; genetics ; Polymorphism, Genetic ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sleep Apnea, Obstructive ; genetics ; Waist-Hip Ratio ; Young Adult