Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis

Abstract

Abstract. The vitamin D receptor (VDR) is an important factor in activating immune response in different infectious diseases. The aim of the present study was to investigate the association between the VDR gene polymorphisms and pulmonary tuberculosis (PTB). The case control study was performed on 120 PTB patients and 131 healthy controls. Genetic analysis was performed by polymerase chain reaction and the restriction fragment length polymorphism method. The VDR Fok1 Ff genotype was associated with TB and the risk of PTB was two times higher in individuals with the Ff genotype. A higher frequency of f allele was observed in PTB patients and therefore, the f allele may be a risk factor for PTB susceptibility. There were no associations between the Taq1 and Bsm1 polymorphisms and PTB. In addition, haplotype analysis showed that the f-T-B and f-t-b haplotypes (Fok1, Taq1 and Bsm1) may have the potential to increase PTB susceptibility. In conclusion, the Ff genotype and f allele of the VDR Fok1 polymorphism were associated with PTB susceptibility. In addition, the f-T-B and f-t-b haplotypes may be the susceptible haplotypes for PTB. IntroductionTuberculosis (TB) is the result of infection with Mycobacterium tuberculosis (M. tuberculosis) and is a significant cause of morbidity and mortality worldwide. Each year >9 million people are infected by TB and >1.7 million succumb to TB annually (1). The incidence of TB in Iran has been reported as 13.7 per 100,000 in 2009; however, its incidence was higher in the Sistan-Balouchestan province, southeastern Iran. The higher incidence is due to bordering with Afghanistan and Pakistan; two countries with a high TB prevalence (2). Cell-mediated immunity is essential for suppression of Mycobacterial infection as it is an intracellular parasite (3). The fact that only 10% of those infected with M. tuberculosis progress to clinical disease revealed that genetic factors, as well as environmental factors are involved in the pathophysiology of TB (4).In addition, the host genetic basis of TB has been confirmed by twin studies that indicated a two times higher risk of disease in identical twins compared to non-identical twins (5).Several genes have been found to play a role in TB susceptibility and the relative significance of these genes in disease progression or various forms of disease is often modified by the ethnicity in different populations (6).The active form of vitamin D, 1-25-dihydroxyvitamin D 3 , is an important hormone that modulates the activity of different defense and immune cells, including lymphocytes, monocytes, macrophages and epithelial cells (7). Since vitamin D 3 increases phagocytosis via the activation of macrophages and affects immune response, it is potentially involved in the development of several diseases (8). Vitamin D 3 may limit the growth of M. tuberculosis in macrophages (7). Vitamin D 3 exerts its effects through the vitamin D receptor (VDR) and regulates numerous target genes by binding to its nuclear receptor. Active VDR binds to vitamin D response...

Association Between Vitamin D Receptor Gene Polymorphisms and Helicobacter Pylori Infection

“…The presence of Single Nucleotide Polymorphisms (SNP) was reported on this gene. The Restriction Fragment Length Polymorphism (RFLP) for FokI, BsmI, ApaI and TaqI restriction enzymes is used nowadays in genetic susceptibility studies of infectious diseases [11]. TaqI polymorphism (rs731236; T>C) results from the change of thymine to cytosine (ATT to ATC).…”

Vitamin D receptor genetic polymorphisms are associated with oral lichen planus susceptibility in a Chinese Han population

“…Evidence from population studies suggests that vitamin D deficiency is highly prevalent among the general population in China, which may be related to genetic variation in VDR [16]. Previous studies have shown that VDR genetic variants (such as rs1544410, rs7975232 and rs731236) can participate in the development of various tumors (such as prostate cancer and hepatocellular carcinoma) by affecting the biological effects of vitamin D [17,18]. Shortly thereafter, vitamin D deficiency was found to be associated to immune-related diseases (systemic lupus erythematosus) and infectious diseases (tuberculosis) [19].…”

Association of VDR gene polymorphisms and 22 bp deletions in the promoter region of TLR2Δ22 (‐196‐174) with increased risk of pulmonary tuberculosis: A case‐control study in tea garden communities of Assam

“…Epidemiological studies have revealed that VDR gene polymorphism is significantly associated with an increased risk of PTB in Venezuela, Iran, Turkey, and Han Taiwanese populations . Molecular epidemiological studies have also revealed that VDR polymorphism is significantly associated with an increased risk of PTB in tribal population of Chhattisgarh and southeastern region of India .…”