The association between BsmI variant of vitamin D receptor gene and susceptibility to tuberculosis.

Vitamin D receptor (VDR) gene variants may play a key role in the susceptibility to tuberculosis (TB). We have investigated the association BsmI, TaqI, FokI polymorphisms in the VDR gene with susceptibility to tuberculosis. This study included 128 patients with TB (pulmonary and extrapulmonary TB) and 80 healthy subjects living in Istanbul, Turkey. Genetic polymorphisms were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques at genomic DNA isolated from whole blood-EDTA. The present study results indicate that the genotype and allele frequencies for patient group (BB:22, Bb:53, bb:25; B allele:48%, b allele:52%) was significantly different from the control group (BB:6, Bb:48, bb: 46; B allele:30 b allele:70) due to an overrepresentation of B allele (P: 0.000 OR: 1.61 95% 1.23-2.11). However there were no significant differences in distribution of allele/genotype frequencies of FokI, TaqI variants between TB and healthy controls. This study results suggest that BsmI variant of VDR gene may play an important role in susceptibility to tuberculosis.

Analysis of transforming growth factor beta 1 (TGF-beta1) gene polymorphisms in Turkish patients with scleroderma.

Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and visceral organs. Fibrosis associated with SSc is characterized by an increased synthesis of a wide range of extracellular matrix (ECM). TGF-beta is a pluripotent cytokine in a wide range of cell types. In particular it has been found to be a potent inducer of ECM protein synthesis and fibroblast migration. The TGF-beta1 gene is highly polymorphic and two signal sequence polymorphisms at codon 10 and codon 25 are linked to disease outcomes. In this study, we analysed two polymorphic sites of the TGF-beta1 gene, codon 10 and codon 25, in 43 Turkish SSc female patients with interstitial lung involvement and in 75 healty individuals by ARMS-PCR. In our study no significant difference was found in codon 10, codon 25 genotype frequencies between patient with SSc and the control group (p = 0.676, 0.375, respectively). Our findings suggest that codon 10 and 25 polymorphism cannot be related with SSc for Turkish population.

NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disease susceptibility in tuberculosis and rheumatoid arthritis.

NRAMP1 gene has multiple pleiotropic effects on macrophage activation pathways. These pleiotropic effects may increase resistance to infections such as tuberculosis (TB), but may also lead to susceptibility of autoimmune diseases such as rheumatoid arthritis (RA). It has been hypothesized that allele 3 would be associated with autoimmune diseases, whereas allele 2 would be associated with infectious diseases, and genetic factors that enhanced survival in the epidemics of TB might have led to susceptibility for the development of RA. We analysed four NRAMP1 gene polymorphisms including 5' promoter (GT)(n) (rs34448891), INT4 (469 + 14G/C) (rs3731865), 3'UTR (1729 + 55del4) (rs17235416) and D543N (codon 543, Asp to Asn) (rs17235409) in 112 patients with TB, 98 patients with RA, 80 healthy controls for TB and 122 healthy controls for RA using ARMS-PCR and PCR-RFLP. We found a significant association between INT4 and RA (P = 0.004, odds ratio: 2.06, 95% CI: 1.24-3.41), but no significant differences between 5' promoter, D543N, 3'UTR polymorphisms and RA. There were no associations between NRAMP1 gene polymorphisms and TB. Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB. INT4 polymorphism may be associated with RA in Turkish patients.

Association between 'interleukin' 10 gene (IL10) polymorphisms and systemic sclerosis with interstitial lung involvement.

Systemic sclerosis (SSc), also termed as "scleroderma", is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Extracellular matrix (ECM) production by fibroblasts in SSc is modulated and regulated by cytokines. Since IL10 has antiinflamatory properties and, contributes to the fibrotic processes in SSc, we analyzed IL-10 gene polymorphisms including -1082 G/A, -819 C/T and -592C/A in 45 systemic sclerosis patients with lung involvement and 150 healthy control using ARMS-PCR. While no association was found between SSc and -819C/T, -592C/A polymorphism, -1082 G/A allele frequency in SSc patients was higher than that in control and significant association was found between SSc and -1082 G/A (Pc: <0.000, OR: 2.85 95% CI: 1.74-4.63). In addition significant difference was found between the frequencies of the IL-10 GCC, ACC haplotypes (Pc: <0.000, OR: 2.85, 95% CI: 1.74-4.63; Pc: 0.012, O.R: 1.56, 95% CI: 1.09-2.23, respectively), GCC(+)/GCC(+), GCC(-)/GCC(-) genotypes (Pc: 0.002, OR: 5.07, 95% CI: 1.82-14.21; Pc: <0.000, O.R: 4.00, 95% CI: 1.87-8.98, respectively) and SSc. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may play role in SSc susceptibility.

Interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10 genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.

NRAMP1 (SLC11A1): a plausible candidate gene for systemic sclerosis (SSc) with interstitial lung involvement.

Systemic sclerosis (SSc), also termed "scleroderma," is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor alpha, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5' promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3'UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.