β防御素-1基因单核苷酸多态性与肺结核易感性的相关性  

Association between human beta defensin-1 single nucleotide polymorphisms and susceptibility to pulmonary tuberculosis

作　　者：吴小脉[1] 龚柳阳[1] 林健[1] 王慧红 

机构地区：[1]浙江省台州医院呼吸科,临海317000 [2]健康管理中心

出　　处：《中华预防医学杂志》2012年第10期912-915,共4页Chinese Journal of Preventive Medicine

基　　金：浙江省台州市科技局资助项目（081KY04）

摘　　要：目的研究β防御素-1基因（DEFB1）5′非编码区SNP与汉族人群肺结核易感性的相关性。方法以病例-对照研究方法，采集102例肺结核患者和148名健康对照者的静脉血，用全血DNA抽提试剂盒提取基因组DNA，高保真酶PCR扩增目标片段，直接测序法检测DEFB1基因-52A／G、-44C／G、-20A／G3个位点的SNP。采用，检验分析基因型、等位基因频率，SHEsis软件分析连锁不平衡和单倍型分布频率。结果肺结核组102例，其中男性69例，女性33例，年龄为（53．42±20．22）岁；对照组148名，其中男性95名，女性53名，年龄为（50．67±14．53）岁，两组间性别、年龄差异无统计学意义（P〉0．05）；DEFB1-44CC基因型频率肺结核组高于对照组[分别为81．4％（83／102）、66．9％（99／148），χ2=5．114，P〈0．05，0R=2．096，95％CI：1．095-4．011]，-44C等位基因频率肺结核组高于对照组[分别为89．2％（182／204）、80．4％（238／296），χ2=6．975，P〈0．05，OR=1．576，95％CI：1．086～2．286]，两组间-52位点各基因型频率和等位基因频率、-20位点各基因型频率和等位基因频率差异无统计学意义（P值均〉0．05）；GGG（-52／-44／-20）单倍型频率肺结核组低于对照组（分别为0．030、0．081，／1（2=5．629，P〈0．05，0R=0．348，95％CI：0．140～0．863），3个位点的SNP未发现存在连锁不平衡（D’值分别为0．132、0．064、0．088，r2值分别为0．003、0．002、0．003，P值均〉0．05）。结论DEFB1因SNP与汉族人群肺结核易感性相关，-44c-GSNP和GGG（-52／-44／-20）单倍型可能在肺结核患病中发挥保护性作用。Objective To investigate the possible association between the SNP in the 5＇ untranslated region （5＇ UTR） of the human beta defensin 1 （DEFB1） gene and the susceptibility to pulmonary tuberculosis （PTB） in Chinese Han population. Methods In this case-control study, venous blood was collected from 102 patients with PTB and 148 healthful persons. Genomic DNA was extracted using whole blood DNA extraction kit. The -52A/G, -44C/G and -20A/G SNP were genotyped by PCR-directed sequencing. The genotypes and allele frequency were analyzed using the χ2 test. The linkage disequilibrium and haplotype were analyzed by SHEsis software. Results A total of 102 patients with PTB （69 males and 33 females, （53.42 ± 20. 22）years old） and 148 healthy control cases （95 males and 53 females, （50.67 ± 14. 53 ） years old） were enrolled, with no difference in gender and age （ all P values 〉 0. 05）. DEFB1 - 44 CC genotype was significantly more frequently found in PTB patients than in control group （81.4% （83/102） vs 66.9% （99/148）,χ2 =5. 114, P〈0.05, OR =2.096, 95% CI： 1. 095 - 4. 011 ）, so was - 44C allele （ 89.2% （182/204） vs 80. 4% （238/296）, χ2 = 6. 975, P〈0.05, 0R=1.576, 95%CI：1.086-2.286）.No difference in -52 A/G and -20 A/G SNP was observed between the two groups. The proportion of the GGG （ - 52/- 44/- 20） haplotype was lower in PTB patients than in the control group （ 0. 030 vs 0. 081, χ2 = 5. 629, P 〈 0. 05, OR = 0. 348, 95% CI： 0. 140 -0. 863）. No linkage disequilibrium was found among the SNP of the three sites（D＇ values were 0. 132, 0. 064, 0. 088 ; r2 values were 0. 003, 0. 002, 0. 003 ; all P values 〉 0. 05 ）. Conclusion These results suggestthat the SNP of DEFB1 5＇ UTR is associated with susceptibility to PTB in Chinese Han population. -44 C→G SNP and the related haplotype （GGG） might play a protective role in the pathogenesis of PTB.

关 键 词：Β防御素 结核 肺 多态性 单核苷酸 

分 类 号：R521[医药卫生—内科学]