甘露聚糖结合凝集素基因多态性对社区获得性肺炎病情程度的评估作用

Evaluation of the mannose-binding lection gene polymorphism on the severity of community acquired pneumonia in adults

目的 研究社区获得性肺炎（CAP）患者甘露聚糖结合凝集素（MBL）结构基因第一外显子54位密码子基因多态性及血清MBL、C-反应蛋白（CRP）水平对疾病严重程度的评估价值.方法 采用前瞻性观察性临床研究方法,选择天津市人民医院住院的汉族成人CAP患者104例,检测MBL 54位密码子点突变频率;进行肺炎严重指数（PSI）评分并分级;于治疗前及治疗4d、7d采用酶联免疫吸附试验（ELISA）检测血清MBL水平,用免疫比浊法检测CRP水平.另外选取100例同地区年龄、性别、民族匹配的健康体检人群作为对照组.比较CAP组与对照组及不同PSI分级CAP患者血清MBL、CRP水平,并进行相关性分析.结果 CAP组与对照组MBL 54位密码子存在GGC→GAC变异,两组MBL 54位密码子野生型及杂合突变型基因型频率（x2=0.018,P=0.893）和等位基因频率（x2=0.019,P=0.903）的分布无统计学差异.CAP组治疗前及治疗4d、7d血清MBL水平（mg/L）先升后降,分别为3.75±1.78、4.53±1.99、4.04±1.91,均明显高于对照组（2.84±1.41,均P＜0.01）;血清CRP水平（mg/L）逐渐下降,分别为66.88±40.47、51.21±37.54、36.91±36.02,均明显高于对照组（6.96±2.19,均P＜0.01）.CAP患者PSI分级Ⅰ级12例,Ⅱ级32例,Ⅲ级20例,Ⅳ级22例,V级18例.不同PSI分级之间（x2=1.210,P=0.876）、普通病房与重症监护病房之间（x2=0.569,P=0.451） MBL 54位密码子基因型分布无统计学意义.CAP患者不同PSI分级之间血清MBL水平在治疗前（F=1.313,P=0.279）、治疗4d（F=1.705,P=0.165）、治疗7 d（F=1.684,P=0.170）差异均无统计学意义;PSIⅡ～V级患者治疗4d时血清MBL浓度较治疗前均明显增高,治疗7d时降至治疗前水平.CAP患者不同PSI分级之间血清CRP水平在治疗前（F=23.179,P=0.000）、治疗4d（F=26.601,P=0.000）、治疗7 d（F=10.358,P=0.000）差异均有统计学意义;PSI各级患者血清CRP水平均随治疗时间逐渐下降,PSI分级越高,血清CRP下降越不明显.CAP患者治疗前及治疗4d、7d时PSI分级与血清MBL均无相关性（治疗前r=-0.205,P=0.145;治疗4 dr=-0.062,P=0.662;治疗7 d r=-0.063,P=0.656）,与血清CRP均呈显著正相关（治疗前r=0.809,P=0.000;治疗4dr=0.842,P=0.000;治疗7 d r=0.702,P=0.000）.结论 MBL 54位密码子基因型对CAP疾病严重程度无影响;CAP患者血清MBL升高并随治疗时间呈动态变化,可作为CAP的炎性标志物,但尚不能用于对CAP疾病严重程度的评估.

Objective To evaluate the significance of the mannose-binding lection （MBL） gene polymorphism at code 54 of exon 1 and MBL serum level and C-reactive protein （CRP） in the severity of community acquired pneumonia （CAP） in adults.Methods A prospective observation was conducted.104 adults Han patients with CAP hospitalized in Tianjin People＇s Hospital were enrolled.Frequencies of MBL54 alleles and genotypes were measured.The patients were evaluated by pneumonia severity index （PSI） score and were graded.Serum MBL was determined by enzyme linked immunosorbent assay （ELISA）,and serum CRP was detected by immunoturbidimetry before and 4 days and 7 days after the treatment.100 healthy control subjects with the same region,age,gender,nationality were enrolled as control group.Serum MBL and CRP levels were compared between CAP group and the control group or among different grades of PSI,and the correlation was analyzed.Results The variation of GGC→GGC in MBL54 was found in CAP patients and controls.Similar frequencies of genotypes （x2=0.018,P=0.893） and alleles （x2=0.019,P=0.903） of MBL54 with wild type and mutant type were found between two groups.The serum MBL level （mg/L） before and 4 days and 7 days after the treatment in CAP group was increased followed by the reduction and they were 3.75 ± 1.78,4.53 ± 1.99 and 4.04 ± 1.91,respectivelv,which were significantly higher than those in control group （2.84 ± 1.41,all P〈0.01）.The serum CRP levels （mg/L） in CAP group were gradually declined,and they were 66.88 ± 40.47,51.21 ± 37.54,36.91 ± 36.02,respectively,which were significantly higher than those in control group （6.96 ± 2.19,all P〈0.01）.There were 12 cases with PSI grade Ⅰ,32 cases with grade Ⅱ,20 cases with grade Ⅲ,22 cases with grade Ⅳ and 18 cases with grade V in CAP patients.There was no significant difference in frequencies of MBL54 genotypes among different grades of PSI （x2=1.210,P=0.876） and between general ward and intensive care unit （x2=0.569,P=0.451）.No differences in the serum MBL level before （F=1.313,P=0.279） and 4 days （F=1.705,P=0.165） and 7 days （F=1.684,P=0.170） after the treatment were found among different PSI grades.The serum MBL level 4 days after the treatment was significantly higher than that before treatment,then decreased to the level before treatment on the 7th day after treatment in CAP patients with grade Ⅱ-Ⅳ.There was significant difference in serum CRP level before （F=23.179,P=0.000） and 4 days （F=26.601,P=0.000） and 7 days （F=10.358,P=0.000） after the treatment among different PSI grades in CAP patients.The serum levels of CRP in patients with different PSI grades were gradually decreased with time prolonged,the higher the PSI grade,the more obscure the serum CRP decrease.No correlation was found between PSI grade and serum MBL before and 4 days and 7 days after the treatment （before treatment：r=-0.205,P=0.145; 4 days after treatment：r=-0.062,P=0.662; 7 days after treatment：r=-0.063,P=0.656）,and positive correlation between PSI grade and serum CRP was found （before treatment：r=0.809,P=0.000; 4 days after treatment：r=0.842,P=0.000; 7 days after treatment：r=0.702,P=0.000）.Conclusions The MBL54 codon genotypes had no effect on the susceptibility of CAP.The serum MBL was elevated and dynamic changes with increasing treatment time in CAP patients were shown.MBL can be used as a reaction of CAP in acute stage.But it cannot be used as an inflammatory marker for the severity of CAP.