ADAM33基因Met764Thr位点多态性与支气管哮喘发病及患者肺功能的相关性

Association of polymorphism of Met764Thr locus allele in ADAM33 gene with bronchial asthma and lung function of asthmatic subjects

目的探讨中国华南地区汉族人群 ADAM33基因 Met764Thr 位点多态性与支气管哮喘(简称哮喘)及其患者肺功能的相关性。方法对164例中国华南汉族哮喘患者(哮喘组)及112名汉族健康者(健康对照组),应用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)、DNA 测序及肺功能测定的方法。结果 (1)不同种族人群 ADAM33基因 Met764Thr 位点等位基因频率的比较差异无统计学意义(X^2=6.77,P>0.05);(2)ADAM33基因 Met764Thr 位点3种基因型(Met764/Met764、Met764/Thr764、Thr764/Thr764)在哮喘组分布频率分别为78.7%(129/164)、18.3%(30/164)、3.0%(5/164);健康对照组分布频率分别为91.1%(102/112)、6.3%(7/112)、2.7%(3/112);各基因型分布频率哮喘组与健康对照组比较差异有统计学意义(X^2=8.46,P<0.05)。ADAM33基因 Met764Thr 位点 Thr764等位基因在哮喘组与健康对照组分布频率分别为0.122、0.058,哮喘组与健康对照组 Met764及 Thr764等位基因频率比较差异有统计学意义(X^2=6.27,P<0.05);(3)单变量Logistic 回归分析 Met764Thr 位点基因多态性与哮喘的关系表明,相对 Met764/Met764基因型而言,Met764/Thr764杂合型与 Met764/Tbr764+Thr764/Thr764基因型均能显著增加哮喘发生的危险性[OR 值及95%可信区间(CI)分别为3.389(1.430～8.030)、2.767(1.308～5.854),P 均<0.05];(4)在哮喘组中3种基因型的用力肺活量(FVC)实测值/预测值%、第一秒用力呼气容积(FEV_1)实测值/预测值%水平比较差异有统计学意义(F 值分别为0.49、5.17,P 均<0.05)。结论 ADAM33基因 Met764Thr 位点基因多态性与中国华南汉族人群哮喘发病及患者的肺功能相关。

Objective To analyze the association of the polymorphism of Met764Thr with bronchial asthma and lung function of asthmatic subjects of Han nationality in Southern China. Methods In 164 unrelated patients with asthma and 112 unrelated healthy controls, polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing were used to determine polymorphism of Met764Thr locus allele in ADAM33 gene. The clinical indexes associated with lung function （FVC%, FEV1 % ） were compared among the three genotypes（ Met764/Met764, Met764/Thr764, Thr764/Thr764）in asthmatic subjects. Results No significant difference was found in the allele （ Met764, Thr 764） frequency among populations in UK, US, German, Korean, and Southern China （χ^2 = 6.77, P 〉 0.05 ） . The frequencies of the genotypes （ Met764/Met764, Met764/Thr764, Thr764/Thr764） were respectively 78.7% （129） ,18.3% （30）,3.0% （5） in 164 asthmatic subjects and respectively 91.1% （102）, 6.3% （7）, 2. 7% （3） in the 112 controls. There was a significant difference in the distributions of the genotypes （ Met764/Met764, Met764/Thr764, Thr764/Thr764） between asthmatic subjects and controls （ χ^2 = 8.46, P 〈0.05）. The frequencies of alleles （Thr764） were respectively 12. 2% in the asthmatic subjects and 5.8% in the controls. Significant difference was observed in the allele （Met764, Thr 764） frequency between the two groups （ χ^2 = 6. 27,P 〈 0. 05）. The presence of Thr764 allele of ADAM33 gene was found to be a greater risk factor in asthmatic subjects than in controls. The odds ratio（OR） of Met764/Thr764 and Met764/Thr764 ＋ Thr764/Thr764 were 3. 389 （ 1. 430 - 8. 030 ） , 2. 767 （ 1. 308 - 5. 854） , respectively. When compared with Met764/Met764 genotype, all P 〈 0. 05. There was a significant decrease in the FVC% and FEV1% levels of Met764/Thr764, Thr764/Thr764 and Met764/Met764 genotype. Conclusions These results suggest that Met764Thr locus genetic polymorphism is associated with susceptibility of asthma and clinical indexes of lung function of asthmatic subjects of Han nationality in Southern China.