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

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（χ^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（χ^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（χ^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／Thr764＋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（FEV1）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。

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

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%, FEV(1)%) 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 (chi(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 (chi(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 (chi(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 FEV(1)% 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.