Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III

Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulin-producing \u3b2 cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a well-known regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a meta-analysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale

FYB polymorphisms in Brazilian patients with type I diabetes mellitus and autoimmune polyglandular syndrome type III

The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays

Commiphora leptophloeos Phytochemical and Antimicrobial Characterization

Commiphora leptophloeos is a plant specie usually known for its medicinal purposes in local communities in Northeast Brazil. In order to evaluate its therapeutic potential, we aimed to determine the phytochemical and antimicrobial properties of C. leptophloeos extracts. Thin Layer Chromatography (TLC) was able to detect the presence of phenolic compounds, flavonoids and reducing sugars. Three phenolic compounds were identified by HPLC and described as Gallic, Chlorogenic and Protocatechuic acids. On the other hand, H(1)NMR analysis revealed the presence of hinokinin, a bioactive lignan further characterized in the present work. The minimum inhibitory concentration (MIC) values for hinokinin ranged from 0.0485 to 3.125 mg/mL in different S. aureus clinical isolates and showed a bactericidal activity against MRSA isolated from blood (MMC 0.40 mg/mL) and postoperative secretion (MMC = 3.125 mg/mL). C. leptophloeos extracts also showed antimicrobial activity against Mycobacterium species such as M. smegmatis (MIC = 12.5 mg/mL) and M. tuberculosis (MIC = 52 mg/mL). Additionally, we determined the toxicity of C. leptophloeos by in vitro HC50 tests with hemolytic activity detected of 313 \ub1 0.5 \u3bcg/mL. Our results showed that C. leptophloeos possesses inhibitory properties against MRSA as well as several other clinically important microorganisms. Furthermore, the present work is the first report of the presence of hinokinin in Commiphora genus

LIG4 and RAD52 DNA repair genes polymorphisms and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with a strong genetic background. Nevertheless, SLE might also be triggered due to environmental factors, such as UV light exposure. DNA double strand breaks (DSBs) may be induced secondarily by UV radiation, increasing DNA immunogenicity and in SLE patients DNA repair is diminished, allowing the accumulation of DSBs and genomic instability. LIG4 and RAD52 genes play important roles in DNA repair mechanisms and a recent microarray analysis showed their differential expression in active SLE patients. In this study we investigated a potential association between LIG4 and RAD52 single nucleotide polymorphisms (SNPs) and SLE predisposition in a Southeast Brazilian population. We assessed four Tag SNPs in LIG4 and three in RAD52 gene region, encompassing most of the gene sequence, in 158 SLE patients and 212 healthy controls. We also performed SNPs analysis considering clinical manifestation, gender and ethnicity in SLE patients. Our data did not show association between LIG4 and RAD52 SNPs and SLE, its clinical manifestations or ethnicity in the tested population. The analysis regarding ethnicity and SLE clinical manifestations indicated Caucasian-derived patients as more susceptible to cutaneous and hematological alterations than the African-derived. To our knowledge, this is the first association study involving LIG4 and RAD52 genes and SLE predisposition

Vitamin D receptor polymorphisms and expression profile in rheumatoid arthritis brazilian patients

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and important joint commitment, being the most common systemic autoimmune disease worldwide. RA displays important genetic background with a variety of genes contributing to the immune balance breakdown. Recent studies have demonstrated that vitamin D, through its receptor (VDR), is able to regulate the immune balance and suppress the autoimmunity process, being a potential target in autoimmune diseases. In the present genetic association study, we assessed 5 Tag single nucleotide polymorphisms (SNPs) (rs11168268, rs2248098, rs1540339, rs4760648 and rs3890733), which cover most of the VDR gene, in three different Brazilian populations (from Northeast, Southeast and South Brazil). We also evaluated the VDR expression profile in whole blood and monocytes from RA patients. For genotyping study, 428 RA patients and 616 healthy controls were genotyped with fluorogenic allele specific probes on an ABI7500 platform. For gene expression study, VDR mRNA levels of 15 RA patients and 26 healthy individuals were assessed by RT-PCR. Our results showed that SNPs rs4760648 and rs3890733 are associated to RA susceptibility (p value = 0.0026, OR 1.31 and p value = 0.0091, OR 1.28 with statistical power = 0.999 and 0.993, respectively). Regarding RA clinical features, the studied SNPs did not show significant associations. The gene expression assays showed that VDR mRNA levels were down regulated in both whole blood (-3.3 fold) and monocytes (-3.2 fold) of RA patients when compared to healthy controls. Our results, the first reported for distinct Brazilian populations, support a role of the VDR gene in the susceptibility to RA