Evaluation of interferon-induced transmembrane protein-3 (IFITM3) rs7478728 and rs3888188 polymorphisms and the risk of pulmonary tuberculosis

Abstract

Abstract. The current study aimed to examine the possible association between the interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample population. This case-control study was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The findings showed no significant association between rs7478728 polymorphism and risk of PTB. Regarding rs3888188 polymorphism, the TG genotype as well as G allele significantly increased the risk of PTB [odds ratio (OR)=2.48, 95% confidence interval (CI): 1.42-4.53; P=0.002, and OR=2.26, 95% CI: 1.33-3.86; P= 0.003, respectively]. In conclusion, the findings revealed that rs3888188 polymorphism increased the risk of PTB in a sample of Iranian population. Additional investigation with larger sample sizes and different ethnicities are needed to verify our findings. IntroductionTuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) infection, is a public health problem globally (1,2). According to the WHO report on the worldwide control of TB, approximately 8.6 million new cases occurred in 2012 (3). Although almost 33% of the population is infected with TB, only 5-10% of infected cases develop active TB (3), which suggests a major role of genetic factors in host immunity.Interferon-γ (IFNγ) is produced and released by host cells in response to the presence of numerous pathogens (4). It plays a key role in macrophage activation during MTB infection (5).Individuals defective in the genes for IFNγ or IFNγ receptor (IFNγR) have been indicated to be susceptible for mycobacterial infections including MTB (6). Previously, we showed an association between IFNγ and IFNγR variants and risk of pulmonary TB (PTB) (7,8).Interferon-induced transmembrane protein-3 (IFITM3) is a double transmembrane protein that can be upregulated by IFNs and participates in INF-triggered processes, such as homotypic cell adhesion, anti-proliferative activities in tumor pathogenesis, and the innate immune response to virus infections (9-13). The IFITM3 gene is mapped to an IFITM gene cluster on chromosome 11p15.5 (14). In a genome wide scan, Stein et al (15) identified that one of the TB-linked loci was located in this chromosome region. To the best of our knowledge, there is only one report regarding the impact of IFITM gene polymorphisms on the risk of TB (16). Therefore, the present study aimed to examine the possible associations between polymorphisms of IFITM3 gene and susceptibility to PTB in a sample of Iranian population. Materials and methodsPatients. This case-control study was performed on 188 PTB patients and 169 age-and gender-matched healthy individuals. The enrollment process and study design are described elsewhere (17-23). Briefly, the cases were chosen from PTB patients admitted to a University-Affiliated Hospital (Bou-Ali Hospital, Zahedan, Iran, referral center for TB) with no clinical sy...

Genetic characteristics and polymorphisms in the chicken interferon-induced transmembrane protein (IFITM3) gene

“…A subsequent study reported that the distribution of rs3888188 SNP in the IFITM3 gene correlated with the number of UC patients (Seo et al 2010;Wu et al 2007). Furthermore, rs3888188 SNP is associated Table 3 Linkage disequilibrium (LD) among fourteen polymorphisms in the chicken IFITM3 gene with the infection rate of tuberculosis and recent studies reported that the IFITM3 protein exhibited a broad spectrum of immune responses to variable pathogens, including not only enveloped viruses but also non-enveloped viruses and bacteria (Anafu et al 2013;Naderi et al 2016;Ranjbar et al 2015).…”

Human genetic factors in tuberculosis: an update

“…Variant rs3794624A/G of the CYBA gene that encodes p22phox, a subunit of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, was associated with susceptibility to TB in Han Chinese and Tibetan populations . SNP rs3888188G/T in the interferon‐induced transmembrane protein‐3 ( IFITM3 ) gene was associated with an increased risk of PTB in an Iranian population . SNP rs1052632A/G in the MR1 gene, which encodes a MHC class I‐related gene protein, was associated with the development of meningeal TB in Vietnamese patients.…”