[NRAMP1基因多态性与中国汉族儿童结核病易感性的关联]

[Association of NRAMP1 gene polymorphisms with the susceptibility to tuberculosis in ethnic Han Chinese children].

作者信息

Jin Jing, Sun Lin, Jiao Wei-Wei, Zhao Shun-Ying, Li Hui-Min, Guan Xiao-Lei, Jiao An-Xia, Chi Wei, Jiang Zai-Fang, Shen A-Dong

机构信息

Beijing Pediatric Research Institute, Beijing Children's Hospital Affiliated to Capital Medical University, Beijing 100045, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2009 Apr;11(4):283-7.

PMID:19374813

Abstract

OBJECTIVE

Tuberculosis is still a public health problem. Host genetic factors, such as polymorphisms in NRAMP1 gene, may play a role in the development of tuberculosis. To clarify the effect of NRAMP1 gene polymorphisms on the development of childhood tuberculosis, the association of NRAMP1 gene polymorphisms with susceptibility to tuberculosis in the ethnic Han Chinese children was investigated.

METHODS

From January 2005 to March 2008, 130 ethnic Han children with tuberculosis (TB group) were enrolled. Three hundred and ninety hospitalized ethnic Han children for physical examination in the surgery department were used as the control group. The controls were matched with tuberculosis children by age, sex and area. PCR-RFLP analysis was performed on DNA samples to identify allele genotypes of INT4 and D543N in NRAMP1 gene. Genotype frequency differences between tuberculosis patients and controls were analyzed using x2 test.

RESULTS

No statistical difference was found in the genotype frequency of variants G/C and C/C at the INT4 locus between the TB and the control groups. At the D543N locus, the frequency of genotype variants (G/A and A/A) was significantly higher in the TB group (34/130) than that in the control group (66/390) (x2=5.349, P<0.05; OR=1.74, 95%CI=1.08-2.79). When stratified by sex, differences in the genotype distribution were observed only in females at the D543N locus, which the variant genotypes were higher in the TB group (16/52) than in the control group (21/155) (x2=7.866, P<0.05; OR=2.84, 95%CI=1.34-5.99). For males, there was no difference between the TB and the control groups. At the INT4 locus, no difference was observed between the two groups in boys and girls.

CONCLUSIONS

Genotypic variation at the D543N locus in NRAMP1 gene may be associated with susceptibility to tuberculosis in ethnic Han Chinese children. Variant genotypes in NRAMP1 gene (G/A and A/A) may be susceptible genotypes to tuberculosis in ethnic Han Chinese children. Girls with variant genotypes were more susceptible to tuberculosis.

摘要

目的

结核病仍是一个公共卫生问题。宿主遗传因素，如天然抵抗相关巨噬蛋白1（NRAMP1）基因多态性，可能在结核病的发生发展中起作用。为阐明NRAMP1基因多态性对儿童结核病发生发展的影响，本研究调查了NRAMP1基因多态性与汉族儿童结核病易感性的关系。

方法

选取2005年1月至2008年3月期间收治的130例汉族结核病儿童作为结核病组（TB组）。选取390例在外科住院体检的汉族儿童作为对照组。对照组在年龄、性别和地区方面与结核病儿童相匹配。对DNA样本进行聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析，以鉴定NRAMP1基因中INT4和D543N的等位基因基因型。采用卡方检验分析结核病患者与对照组之间基因型频率的差异。

结果

TB组与对照组在INT4位点的G/C和C/C变异基因型频率上无统计学差异。在D543N位点，TB组（34/130）的变异基因型（G/A和A/A）频率显著高于对照组（66/390）（χ2 = 5.349，P < 0.05；比值比（OR）= 1.74，95%置信区间（CI）= 1.08 - 2.79）。按性别分层时，仅在女性中观察到D543N位点基因型分布存在差异：TB组（16/52）的变异基因型高于对照组（21/155）（χ2 = 7.866，P < 0.05；OR = 2.84，95%CI = 1.34 - 5.99）。男性的TB组与对照组之间无差异。在INT4位点，男孩和女孩两组之间均未观察到差异。