NRAMP1基因多态性与中国汉族儿童结核病易感性研究

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

摘要:

目的：结核病在全球具有死灰复燃的趋势，宿主遗传因素在结核病发生、发展中的作用越来越受到人们的重视，NRAMP1基因多态性可能参与结核病的发病。该研究探讨NRAMP1基因多态性与中国汉族儿童结核病易感性的相关关系。方法：病例组为2005年1月至2008年3月北京儿童医院收治的汉族儿童结核病人130例，另选390例外科术前体检儿童，按照年龄、性别、民族以及地区与病例组进行匹配。应用PCR-RFLP分析方法，分别对NRAMP1基因INT4和D543N位点多态性与儿童结核病易感性进行相关分析。结果：NRAMP1基因D543N位点变异型基因型（G/A和A/A）频率，病例组（34/130）明显高于对照组（66/390），差异显著（χ2＝5.349, P<0.05；OR=1.74，95%CI=1.08~2.79）；INT4位点没有统计学差异。分析不同性别的影响，显示D543N位点变异型基因型在病例组女患儿（16/52）明显高于对照组（21/155），差异有显著性（χ2=7.866，P<0.05，OR=2.84，95%CI=1.34~5.99）；而病例组中的男患儿（18/78）和对照组（45/235）之间差异无显著性；INT4 位点无论男还是女都没有差异。结论：NRAMP1基因D543N位点变异与中国汉族儿童结核病易感性存在相关；D543N位点G/A和A/A基因型可能是中国汉族儿童结核病的易感基因型，NRAMP1变异型基因型更易导致女孩患结核病。［中国当代儿科杂志，2009，11（4）：283-287］

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 χ2 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) (χ2＝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) (χ2＝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.［Chin J Contemp Pediatr, 2009, 11 (4):283-287］