汉族459例结核病易感基因多态性与临床特征的相关性

The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in 459 Han patients

目的探讨汉族人群结核病易感基因多态性与临床特征的相关性。方法收集2007年1月至2008年12月上海市肺科医院收治的459例汉族结核病住院患者，分析结核病患者的临床特征（性别、发热、病灶范围、空洞、咯血、初治或复治），采用多种单核苷酸多态性分型技术，检测其维生素D受体（VDR）基因FokI位点和TaqI位点，自然抗性相关巨噬细胞蛋白1（NRAMP1）基因D543N、INT4和3’UTR位点，甘露糖结合凝集素（MBL）基因HL、YX和QP位点，以及吖一干扰素编码（IFNG）基因874AT位点，并对上述基因进行分型。采用单因素方差分析检验基因多态性与临床特征的相关性。结果结核病发热患者VDR基因FokI位点CC、CT和TT基因型的变异率分别为54．7％（29／53）、13．2％（7／53）和32．1％（17／53），不发热患者分别为40．6％（52／128）、30．5％（39／128）和28．9％（37／128），差异有统计学意义（χ2=6．183，P〈0．05）；CT基因型患者出现发热症状的比例为15．2％（7／46），非CT基因型患者出现发热症状的比例为34．1％（46／135），差异有统计学意义（χ2=5．891，P〈0．05），提示CT基因型患者更少出现发热症状；MBL基因QP位点的TT＋TC和CC基因型变异率，结核病初治患者分别为28．3％（60／212）和71．7％（152／212），复治患者分别为19．1％（41／215）和80．9％（174／215），差异有统计学意义（χ2=5．038，P〈0．05）。其余各位点基因型与结核病临床特征均无相关性（χ2值为0．001～2．732，均P〉0．05）。结论VDR基因FokI位点多态性可能与结核病发热症状具有相关性，其中CT变异对结核病患者发热可能具有保护作用，MBL基因QP位点多态性可能与结核病复发有相关性。

Objective To study the correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in Han population. Methods Four hundred and fifty-nine tuberculosis inpatients of Han population in Shanghai Pulmonary Hospital from Jan 2007 to Dec 2008 were recruited. The clinical characteristics of tuberculosis （gender, fever, extent of lesions, cavity formation, hemoptysis, initial treatment and retreatment） were observed. The polymorphisms of VDR gene （variants in Fok I and Taq I ）, NRAMP1 gene （variants in INT4, D543N and 3 UTR）, MBL gene （variants in HL,YX and QP） and IFNG gene （variants in 874AT） were genotyped by a variety of SNP genotyping techniques. The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of the disease was analyzed by ANOVAs. Results The frequency of CC, CT and TT variants of Fok I in VDR gene in cases with fever were 54. 7% （29/53）, 13.2% （7/53） and 32. 1% （17/53）, respectively, compared to40.6% （52/128）, 30. 5% （39/128）and28.9% （37/128） in cases without fever, the difference being significant （ χ2 = 6. 183, P 〈 0. 05 ） . In patients with CT variants, 15.2% （7/46） had fever, while in patients with non-CT variants, 34. 1% （46/135） had fever （χ2 =5. 891, P 〈 0. 05）, suggesting that patients with CT variants were less likely to have fever. The frequencies of TT ＋ TC and CC variants of QP in the MBL gene in initial treatment cases were 28.3% （60/ 212） and 71.7% （ 152/212）, respectively, compared to 19. 1% （41/215） and 80. 9% （174/215） in retreatment cases, the difference being significant （ χ2= 5. 038, P 〈 0. 05 ）. No significant correlation was observed between the other variants and the clinical characteristics of tuberculosis （ χ2 = 0. 001 - 2. 732, P 〉 0.05）. Conclusions The polymorphisms of Fok I in VDR gene was associated with fever among the clinical characteristics of tuberculosis, and patients with CT variants might be protected from fever. The polymorphisms of QP in MBL gene might be associated with recurrence of tuberculosis.