肿瘤坏死因子基因多态性与阻塞性睡眠呼吸暂停低通气综合征

目的探讨肿瘤坏死因子α(TNF-α)启动子上游308位点(TNF-αG-308A)多态性与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的关系。方法研究对象为2004年6月至2005年12月我院睡眠检测中心就诊的患者。采用酶联免疫吸附测定(ELISA)法测定76例 OSAHS 组和42例非OSAHS 对照组血清中 TNF-α水平,并对76例中的18例患者进行持续气道正压通气(CPAP)治疗,测定治疗1个月后患者血清中 TNF-α水平;采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测76例患者 TNF-αG-308A 基因多态性频率及分布,分析该基因多态性与体重指数(BMI)、颈围、腰臀比、多导睡眠图监测(PSG)相关参数以及收缩压、舒张压等的关系。结果 OSAHS 组 TNF-α的血清水平[(12.32±3.62)ng/L]较对照组[(8.59±1.62)ng/L]明显增高(t=7.716,P<0.01);18例患者进行 CPAP 治疗1个月后血清中 TNF-α水平下降为(10.31±1.91)ng/L,但仍未恢复至正常水平;OSAHS 组 AA/AG 基因型频率(31/76,41%)显著高于对照组(7/42,17%;X~2=7.485,P<0.05),其 A 等位基因频率(39/152,25.7%)高于对照组(39/152,9.5%),差异有统计学意义(X~2=8.830,P<0.01)。OSAHS 组 AA/AG 基因型患者血清中 TNF-α水平、颈围、腰臀比、呼吸暂停低通气指数(AHI)[分别为(13.39±3.71)ng/L、(45.2±4.2)cm、(0.91±0.12)和(34.8±15.6)次/h]均高于 GG 基因型[分别为(11.09±3.54)ng/L、(42.7±4.9)cm、(0.85±0.12)和(26.4±12.3)次/h],而最低血氧饱和度(LSaO_2)前者低于后者[(78.8±10.9)%,(83.4±8.6)%],差异均有统计学意义(t 值分别为2.725,2.278,2.150,2.609,2.039;P<0.05或<0.01);BMI、收缩压、舒张压比较差异无统计学意义。结论 OSAHS 的发病与 TNF-αG-308A 基因多态性相关,该基因多态性可能在一定程度上增加了 OSAHS 的遗传易感性。

The relationship between tumor necrosis factor-α gene promoter polymorphism and obstructive sleep apnea-hypopnea syndrome

OBJECTIVE: To investigate the relationship between tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphism and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: The plasma TNF-alpha level of OSAHS group and non-OSAHS group was detected by enzyme-linked immunosorbent assay (ELISA). Eighteen patients with severe OSAHS were treated with continuous positive airway pressure (CPAP) for 1 month, and the serum levels of TNF-alpha was also measured. The genotypes of TNF-alpha gene promoter polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). The genotypes and allele of the polymorphisms 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/hip rate (WHR), polysomnography (PSG), systolic blood pressure (SBP), diastolic blood pressure (DBP) were analyzed. RESULTS: The plasma level of TNF-alpha in OSAHS group was higher than the control group [(12.3 +/- 3.62) ng/L and (8.59 +/- 1.62) ng/L, respectively, t = 7.716, P < 0.01]. CPAP significantly decreased the serum levels of TNF-alpha, but its level (10.31 +/- 1.91) ng/L was still higher in the patients than the control group. The frequencies of TNF-alpha AA/AG genotype in OSAHS group (frequencies 31/76, 40.8%) was higher than the control one (frequencies 7/42, 16.7%) (chi(2) = 7.485, P < 0.05). Statistical analysis showed that OSAHS group had a significantly higher TNF-alphaA allele frequency (frequencies 39/152, 25.7%) than that of the control one (frequencies 39/152, 9.5%) (chi(2) = 8.830, P < 0.01). The OSAHS patients with AA/AG genotype had significantly higher serum levels of TNF-alpha, NC, WHR and aphea-hypopnea index [(13.39 +/- 3.71) ng/L, (45.2 +/- 4.2) cm, (0.91 +/- 0.12), and (34.8 +/- 15.6)/h, respectively] than those with GG genotype group [(11.09 +/- 3.54) ng/L, (42.7 +/- 4.9) cm, (0.85 +/- 0.12) and (26.4 +/- 12.3)/h, respectively] (t = 2.725, 2.278, 2.150, 2.609 respectively, P < 0.05 or < 0.01). The L SaO(2) (the lowest SaO(2)) in patients with AA/AG genotype [(78.8 +/- 10.9)%] was significantly lower than that in patients with GG genotype [(83.4 +/- 8.6)%] (t = 2.039, P < 0.05). There was no significant difference in BMI, SBP and DBP. CONCLUSION: The presence of the TNF-alphaA allele may be associated with susceptibility to OSAHS, and it maybe an important candidate gene for OSAHS.