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

Humans ; Genome-Wide Association Study ; Sleep Apnea, Obstructive/genetics*

OBJECTIVE: To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). METHODS: The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. RESULTS: Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN)₇, (GCN)₁₃, (GCN)₁₄, (GCN)₁₅ and (GCN)₂₀. The frequency of the (GCN)₂₀ allele was the highest (94.79%). And five genotypes were identified, which included (GCN)₇/(GCN)₂₀, (GCN)_13/(GCN)₂₀, (GCN)₁₄/(GCN)₂₀, (GCN)₁₅/(GCN)₂₀, (GCN)₂₀/(GCN)₂₀. The homozygous genotypes were all (GCN)₂₀/(GCN)₂₀, and the carrier rate was 89.58%. Four GCN sequences of the (GCN)₂₀ homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the,Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN)₂₀/(GCN)₂₅ and (GCN)₂₀/(GCN)₃₀, respectively. CONCLUSION It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.
Humans ; Infant, Newborn ; Homeodomain Proteins/genetics* ; Hypoventilation/congenital* ; Mutation ; Sleep Apnea, Central/genetics* ; Transcription Factors/genetics*

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

OBJECTIVE To report on the phenotype of an infant with central hypoventilation syndrome (CCHS) and result of PHOX2B gene mutation analysis for the purpose of genetic counseling and prenatal diagnosis. METHODS Clinical data of an infant with CCHS was collected and analyzed. Potential mutation of PHOX2B gene was analyzed by amplified fragment length polymorphism (amp-FLP) and DNA sequencing. RESULTS The patient had typical clinical features of CCHS including frequent hypoventilation during sleeping, hypoxemia and hypercapnia which could be corrected by continuous ventilatory support. She also had repeated bruising and was difficult-to-wean, but without any cardiac, pulmonary, neuromuscular or brainstem lesions. DNA sequencing and amp-FLP of the PHOX2B gene showed that the patient has carried a polyalanine expansion repeat mutation (PARM) in exon 3. A 27 bp duplication was confirmed in the repeat sequence of 20 alanines by cloned and sequenced. This has led to an expansion of the repeat tract to 29 alanines. The genotype was therefore 20/29. CONCLUSION A patient with CCHS has been described. Mutation screening of PHOX2B gene can be used as an important support for diagnosis and genetic counseling for such patients.
Female ; Homeodomain Proteins ; genetics ; Humans ; Hypoventilation ; congenital ; genetics ; Infant, Newborn ; Mutation ; Sleep Apnea, Central ; genetics ; Transcription Factors ; genetics

Homeodomain Proteins ; genetics ; Humans ; Infant, Newborn ; Male ; Mutation ; Promoter Regions, Genetic ; Sleep Apnea, Central ; congenital ; genetics ; Syndrome ; Transcription Factors ; genetics

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

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

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

Apnea of prematurity (AOP) is one of the common diseases in preterm infants. The main cause of AOP is immature development of the respiratory control center. If AOP is not treated timely and effectively, it will lead to respiratory failure, hypoxic brain injury, and even death in severe cases. Caffeine is the first choice for the treatment of AOP, but its effectiveness varies in preterm infants. With the deepening of AOP research, more and more genetic factors have been confirmed to play important roles in the pathogenesis and treatment of AOP; in particular, the influence of single nucleotide polymorphism on the efficacy of caffeine has become a research hotspot in recent years. This article reviews the gene polymorphisms that affect the efficacy of caffeine, in order to provide a reference for individualized caffeine therapy. Citation.
Apnea/genetics* ; Caffeine/therapeutic use* ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Infant, Premature, Diseases ; Polymorphism, Single Nucleotide