摘要目的 探讨MD-1基因的单核苷酸多态性与华南汉族成人支气管哮喘(简称哮喘)发病及肺功能的相关性.方法 选取2006年2月至2010年2月南方医院确诊的华南汉族成人哮喘患者332例[男169例,女 163例,平均年龄(44±16)岁]作为病例组,选取同期健康查体者276例[143例,女 133例,平均年龄(45±15)岁]作为对照组,利用MassARRAY-IPLEX技术和基质辅助激光解吸电离飞行时间质谱平台(MALDI-TOF-MS)对MD-1基因的rs2233128和rs7740529位点进行基因分型,并对其中105例初次确诊哮喘患者的肺功能进行检查.结果 在华南汉族人群中MD-1的rs2233128位点检出 AG和GG两种基因型,rs7740529位点检出CC、CT和TT 3种基因型,分型成功率为94.74%.与对照组比较,病例组rs2233128的基因型分布(x2=0.030,P=0.863)和等位基因分布(x2=0.029,P=0.865)差异均无统计学意义,而rs7740529的基因型分布(x2=8.681,P=0.013)和等位基因分布(x2=8.005,P=0.005)差异均有统计学意义.与TT基因型比较,rs7740529的CC和CC+CT基因型均能显著增加哮喘发生的危险性,OR值(95%可信区间)分别为2.451(1.299～4.963)和2.172(1.173～4.020).在初次确诊的105例哮喘患者中,rs7740529的3种不同基因型(CC、CT和TT)患者的FVC占预计值%(F=18.405,P=0.000)和FEV1占预计值%(F=25.700,P=0.000)差异均有统计学意义,与TT基因型[(86±9)%,(88±8)%]相比,CC基因型患者的FVC占预计值%[(65±12)%]和FEV1占预计值%[(64±11)%]下降最明显(均P＜0.05),但在初诊为哮喘且病情严重程度不同分级患者的rs7740529基因型分布比较,差异无统计学意义(x2=5.017,P=0.081).结论 MD-1可能是华南汉族成人哮喘的易感基因,rs7740529位点的基因型分布可能与初诊哮喘患者的肺功能改变有关.

abstractsObjective To investigate the correlation between MD-1 gene single nucleotide polymorphism ( SNP ) and bronchial asthma in adults of the Han nationality in Southern China as well as their lung functions. Methods From 2006 to 2010, 332 adult asthmatic patients of the Han nationality diagnosed in Nanfang Hospital, Southern Medical University, and 276 healthy volunteers were recruited for the study. The SNPs of MD-1 gene loci rs2233128 and rs7740529 were genotyped by using MassARRAYIPLEX technology and matrix-assisted laser desorption ionization time of flight mass spectrometry platform (MALDI-TOF-MS). In addition, the lung function of 105 cases initially diagnosed with asthma was measured. Results There was no significant difference in sex ( x2 = 0. 50, P = 0. 824 ) and age ( t = 0. 930,P =0. 357 ) between the asthma and the healthy groups. Genotypes AG and GG were detected in MD-1 gene at rs2233128 locus and genotypes CC, CT and TT at rs7740529 locus in this Han population at SouthernChina. Genotyping success rate was 94. 74%. The rs2233128 genotype distribution ( x2 = 0. 030, P =0. 863 ) and allele ( x2 = 0. 029, P = 0. 865 ) showed no significant difference between the asthma and the control groups. However, the rs7740529 genotype distribution ( x2 = 8. 681, P = 0. 013 ) and allele ( x2 =8.005,P = 0.005) were significantly different in the asthma group as compared to the control group.Compared with the TT genotype, the rs7740529 of the CC and CC + CT genotypes could dramatically increase the risk of asthma, the odds ratio (95% confidence interval) being 2. 451 (1. 299 -4. 9626) and 2. 172 ( 1. 173 - 4. 020 ), respectively. In the 105 patients initially diagnosed with asthma, FVC% and FEV1 % were significantly different among the 3 different genotypes (CC, CT and TT) of the rs7740529 locus (F= 18.405, P=0.000 and F=25. 700, P=0.000). The percentages of predicted value of FVC and FEV1were decreased [ ( 65 ± 12 ) %, ( 64 ± 11 ) % ] in the CC genotype as compared to the TT genotypes [ ( 86 ±9) %, (88 ± 8) % ], P ＜ 0. 05. There was no significant difference of genotype distribution of rs7740529 in different grades of severity of newly diagnosed asthma ( x2 =5. 017 ,P =0. 081 ). Conclusions MD-1 may be a susceptible gene for adult asthma in a Southern Han population in China. Genotype distribution of rs7740529 locus in newly diagnosed patients with asthma may be related to their lung function changes.