An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population

Linlin Wu; Haijun Deng; Yihui Zheng; Mikael Mansjö; Xubin Zheng; Yi Hu; Biao Xu

doi:10.1016/j.ijid.2015.08.003

An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population

Int J Infect Dis. 2015 Sep:38:129-35. doi: 10.1016/j.ijid.2015.08.003. Epub 2015 Aug 7.

Authors

Linlin Wu¹, Haijun Deng², Yihui Zheng², Mikael Mansjö³, Xubin Zheng¹, Yi Hu⁴, Biao Xu¹

Affiliations

¹ 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.
² Disease Control and Prevention Center, Putuo District, Shanghai 200062, China.
³ The Public Health Agency of Sweden (former Swedish Institute for Communicable Disease Control), Solna, Sweden.
⁴ 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.

PMID: 26261060
DOI: 10.1016/j.ijid.2015.08.003

Abstract

Objectives: 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.

Keywords: MBL; NRAMP1; Polymorphism; Susceptibility; Tuberculosis; VDR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Asian People / genetics
Case-Control Studies
Cation Transport Proteins / genetics*
China
Female
Genetic Predisposition to Disease*
Genotype
Haplotypes
Humans
Male
Mannose-Binding Lectin / genetics*
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide*
Polymorphism, Single-Stranded Conformational
Receptors, Calcitriol / genetics*
Tuberculosis, Pulmonary / epidemiology
Tuberculosis, Pulmonary / genetics*

Substances

3' Untranslated Regions
Cation Transport Proteins
Mannose-Binding Lectin
Receptors, Calcitriol
VDR protein, human
natural resistance-associated macrophage protein 1