An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population.
OBJECTIVE
To investigate natural-resistance-associated macrophage protein 1 (NRAMP1), mannose-binding lectin (MBL), vitamin D receptor (VDR) gene polymorphisms and their interaction with susceptibility to pulmonary tuberculosis (PTB) in a Chinese population.


METHODS
A case-control study was conducted in PTB (n=151), age- and sex- matched healthy controls (HCs) (n=453). Genetic polymorphisms of NRAMP1 (INT4, D543NA and 3'UTR), MBL (HL, PQ, XY and AB) and VDR (FokI and Taq) were analyzed by using PCR-restriction fragment length polymorphism (RFLP) and PCR- single- strand conformation polymorphism (SSCP) techniques. Multifactor dimensionality reduction (MDR) analysis was carried out to assess the effects of the interaction between SNPs.


RESULTS
The distribution of NRAMP1- 3'UTR (TGTG/del), MBL- HL (H/L) and FokI (F/f) were significantly different between PTB patients and HCs (p<0.05). HPYA (OR: 1.88; 95% CI: 1.22-2.91), LPXA (OR: 3.17; 95% CI: 1.69- 5.96), LQYA (OR: 3.52; 95%CI: 1.50-8.23) and LPYB (OR: 12.37; 95%CI: 3.75- 40.85) of MBL were risk haplotypes for PTB. The TGTG- H- f (OR: 1.70; 95%CI: 1.10-2.62) and del- H-f (OR: 3.48; 95% CI: 1.45-8.37) of 3'UTR- HL- FokI were also high-risk haplotypes associated with tuberculosis.


CONCLUSIONS
Our study suggests that genotypes of many polymorphic genes are associated with TB, it is necessary to further explore the mechanism of genotypes and gene-gene interaction in susceptibility to tuberculosis.
Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China.
Linlin
L
Wu
Disease Control and Prevention Center, Putuo District, Shanghai 200062, China.
Haijun
H
Deng
Disease Control and Prevention Center, Putuo District, Shanghai 200062, China.
Yihui
Y
Zheng
The Public Health Agency of Sweden (former Swedish Institute for Communicable Disease Control), Solna, Sweden.
Mikael
M
Mansjö
Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China.
Xubin
X
Zheng
Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China. Electronic address: yhu@fudan.edu.cn.
Yi
Y
Hu
Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China.
Biao
B
Xu
D020413:3' Untranslated Regions; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D018167:Receptors, Calcitriol / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
D020413:3' Untranslated Regions; D027682:Cation Transport Proteins; D037601:Mannose-Binding Lectin; D018167:Receptors, Calcitriol; D000099173:Natural Resistance-associated Macrophage Protein 1; C579457:VDR protein, human
MBL; NRAMP1; Polymorphism; Susceptibility; Tuberculosis; VDR