Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population.
BACKGROUND
Increased 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.


METHODS
The 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).


RESULTS
The 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).


CONCLUSIONS
The NADPH oxidase subunit p22phox gene polymorphism may be associated with susceptibility to OSAHS, and it may be an important candidate gene for OSAHS.
Liu
Hui-Guo
HG
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease, Ministry of Health, Wuhan, Hubei 430030, China. hgliu@tjh.tjmu.edu.cn
Liu
Kui
K
Zhou
Yan-Ning
YN
Xu
Yong-Jian
YJ
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002681:China / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000235:genetics*; D049629:Waist-Hip Ratio; D055815:Young Adult
D019255:NADPH Oxidases; C086986:CYBA protein, human