The Role Of Tumor Necrosis Factor Gene Promoter Polymorphism In The Development Of Obstructive Sleep Apnea-hypopnea Syndrome

Part1:An investigation of the relationship between tumor necrosis factorαgene promoter polymorphism and obstructive sleep apnea-hypopnea syndrome【Objective】To investigate the relationship between tumor necrosis factorα(TNF-α) gene promoter polymorphism and obstructive sleep apnea-hypopnea syndrome(OSAHS).【Methods】The plasm TNF-αlevel of subjects are detected by ELISA-kit. 18 patients with the severe OSAHS were treated with CPAP for 1 month,and the serum levels of TNF-alpha were also measured.The genotypes of tumor necrosis factorαgene promoter polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP). The genotypes and allele of the polymorphism were compared between OSAHS group and non-OSAHS group. The effects of the polymorphisms in OSAHS group on body mass index(BMI),neck circumference(NC),waist/hiprate(WHR),polysomnography(PSG), sysstolic blood pressure (SBP),diastolic blood pressure(DBP) were analysed.【Results】The plasm level of TNF-αin OSAHS group is higher than the control group(p<0.01).CPAP significantly decreased serum levels of TNF-α,but serum levels of TNF-αstill is higer than control group.The frequencies of TNF-αAA/AG genotype in OSAHS group is higher than control one(P<0.01).Statistical analysis showed that OSAHS group had a significantly higher TNF-αA allele frequency than that of the control one(P<0.01).The OSAHS patients with AA/AG genotype had significantly larger NC and WHR than the GG genotype group(P<0.05),and they had higher AHI,LaO2(the lowest SaO2)and serum levels of TNF-α(P<0.05).There was no significant difference in BMI ,SBP and DBP.【Conclusions】The presence of the TNF-αA allele may be associated with the susceptibility to OSAHS,and it maybe an important candidate gene for OSAHS.Part2:The expression and relationship of TNF-αand NF-κB in PMBCs of obstructive sleep apnea-hypopnea syndrome patients.【Objective】To study the TNF-αand NF-κB production of peripheral blood mononuclear cells(PMBCs) with OSAHS patients,and to explore their relationship. 【Method】Based on the results of sleep-monitoring,the subjects were divided into two groups: healthy control group and OSAHS group,and the OSAHS group were divided into the mild group, the moderate group and the severe group. The level of NF-κB in PMBCs were tested by Western blot. The serum level of TNF-αand TNF-αmRNA of PMBCs were determined by ELISA Kits and reverse transcription-polymerase chain reaction(RT-PCR),respectively.18 patients with severe OSAHS were treated with CPAP for 1 month,and the serum levels of TNF-αwere also measured.【Results】The level of NF-κB in PMBCs,TNF-αmRNA of PMBCs and the serum levels of TNF-αwith OSAHS were significantly higher than the control group. There were significantly differences between the mild group,the moderate group and the severe group in the level of NF-κB in PMBCs,TNF-αmRNA of PMBCs and the serum levels of TNF-α. There were positive correlations between the level of NF-κB in PMBCs and TNF-αmRNA of PMBCs,the serum levels of TNF-α, respectively.AHI of the OSAHS patiets was positively correlated with the level of NF-κB in PMBCs,TNF-αmRNA of PMBCs and the serum levels of TNF-α. LSaO2 was positively correlated with the level of NF-κB in PMBCs.【Conclusion】NF-κB may be an important upstream regulatory factor ,and promote the expression of TNF-α. Simultaneously the expression of NF-κB indicated the degree of OSAHS in a certain extent.