HLA-Cw基因多态性与肺结核易感性关系的初步研究

A preliminary study on the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis

目的 分析人白细胞抗原（HLA） -Cw基因多态性与肺结核遗传易感性的关系,探究肺结核的易感基因和抵抗基因.方法 选取2010年5月至2011年5月山东省胸科医院确诊的继发性肺结核患者112例为肺结核组,其中男62例,女50例；年龄19 ～ 69岁,平均41.7岁；根据痰涂片抗酸染色结果分为涂阴组77例和涂阳组35例.对照组为同期在该院健康体检的110名,其中男59名,女51名；年龄21 ～ 67岁,平均38.3岁.提取基因组DNA,扩增HLA-Cw等位基因,进行Hardy-Weinberg吻合度检验,估算基因频率（％）=1 -（1-表型频率）1/2.两组间比较采用x2检验,检验水准α/8=0.00625,P＜0.00625为差异有统计学意义.结果 肺结核组HLA-Cw08等位基因的基因频率（43.6％,75/112）显著高于对照组（27.4％,52/110）,差异有统计学意义（x2=8.790,P＜0.00625）；肺结核涂阳组HLA-Cw04等位基因的基因频率（20.7％,13/35）显著高于涂阴组（4.7％,7/77）,HLA-Cw08等位基因的基因频率（22.5％,14/35）显著低于涂阴组（54.4％,61/77）,差异均有统计学意义（x2值分别为12.909和16.732,均P＜0.00625）.结论 HLA-Cw基因多态性与肺结核有一定相关性,HLA-Cw08可能是肺结核的易感基因,HLA-Cw04和08等位基因可能与MTB的感染状态和结局有关.

Objective To analyze the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis （ PTB）,and therefore to explore the susceptible or resistant genes of PTB.Methods A hundred and twelve patients who were confirmed to have secondary PTB in Shandong Chest Hospital from May 2010 to May 2011 were selected as the PTB group,including 62 males and 50 females aged 19-69 years （mean 41.7）.According to the acid-fast staining results,PTB patients were divided into a smear-negative group （SN group,77 cases） and a smear-positive group （SP group,35 cases）.A hundred and ten subjects who underwent physical examination in Shandong Chest Hospital at the same period were selected as the control group,including 59 males and 51 females aged 21 - 67 years （ mean 38.3）.After genomic DNA was extracted,genotyping of HLA-Cw was conducted by sequence specific primer polymerase chain reaction （PCR-SSP） method.Then Hardy-Weinberg （H-W） equilibrium was tested,and gene frequencies （ % ） were estimated =1 - （ 1 - phenotype frequencies） 1/2.Gene frequencies were compared between the PTB group and the control group,and between the SN group and SP group by x2 test.According to Bonferroni＇ s principle,α was divided by the number of alleles （ n =8 ）,and P 〈0.00625 was regarded as statistically significant.Results The frequency of HLA-Cw08 was significantly higher in PTB patients （43.6%,75/112） compared with the controls （27.4%,52/110）,x2 =8.790,P 〈 0.006 25. Among PTB patients,HLA-Cw04 had a significantly higher frequency in the SP group （20.7%,13/35） than in the SN group （4.7%,7/77）,while HLA-Cw08 had a significantly lower frequency in the SP group （22.5%,14/35） than in the SN group （54.4%,61/77）,x2 =12.909,16.732,both P 〈 0.006 25.Conclusions HLA-Cw polymorphism is related to susceptibility to PTB.HLA-Cw08 may be one of the susceptible genes for PTB,and HLA-Cw04 and 08 may be related to MTB infectious status and clinical outcomes.