Obesity is associated with IL-6 gene polymorphisms rs1800795 and rs1800796 but not SOCS3 rs4969170.

BACKGROUND: An imbalance of inflammatory factors can stimulate obesity by inducing chronic inflammation in adipose tissue. Interleukin-6 (IL-6) is a cytokine with both inflammatory and anti-inflammatory functions. Suppressor of cytokine signaling 3 (SOCS3) acts as an inhibitor for a number of cytokine signals. The IL-6 and SOCS3 genes are known to be involved in lipid and energy metabolism, although it is unclear how these genes relate to obesity. The aim of this study is to determine whether the obesity risk is associated with the IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) gene polymorphisms. METHODS AND RESULTS: Based on their body mass index (BMI) scores, 185 people were determined, of whom 90 were from the control group and 95 were obese. Anthropometric measurements and biochemical parameters of the study subjects were documented during the examination. Genomic DNA isolation was performed from the blood samples of all participants. IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) polymorphisms were detected by real-time quantitative polymerase chain reaction (qRT-PCR) from genomic DNA samples. The IL-6 rs1800795 and rs1800796 variants showed a significant difference between the control and obese groups (p = 0.027; p = 0.013). The SOCS3 rs4969170 variation did not substantially differ between the control and obese groups (p = 0.825). CONCLUSION: In our study, IL-6 rs1800795(G/C) and rs1800796(G/C) polymorphisms appeared to be a risk factor for obesity. The C allele was associated with the obesity phenotypes. However, the SOCS3 rs4969170 (A/G) polymorphism was not linked to an increased risk of obesity. IL-6 polymorphisms may be new targets for obesity treatment.

Frequency of myelin oligodendrocyte glycoprotein antibodies in pediatric onset multiple sclerosis.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients might be more likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in pediatric onset MS (POMS). MATERIAL AND METHODS: Patients who experienced their first acute demyelinating event before age 18 years and were diagnosed with MS during follow-up were included in this single-center study. Patient data were retrieved from clinical records. Serum samples obtained and frozen at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted of patients referred to pediatric neurology for headache or vertigo and who had no neurological disorder (n = 48). Another control group consisted of patients with systemic inflammatory disorders systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic. RESULTS: The patient group (n = 122, F/M: 90/32, mean age 17.8 ± 2.6 years) were initially diagnosed as: MS, 62/122 (50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome, 9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received the final diagnosis of POMS. Serum was sampled 22.4 ± 29.2 (0-132) months after the first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%) POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly below the cut-off. These three patients' initial and final diagnoses were MS, their annualized relapsing rates (ARRs) were 0.4-0.6, and most recent Expanded Disability Status Scale was 0. CONCLUSION: Low titers of MOG-Ab can be detected in a small number of POMS patients at similar frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar findings or seizures and had low ARR. Further series and longer follow-up will define whether these cases differ significantly from MOG-Ab negative POMS cases.

Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies.

Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.

COX-1, COX-2 and CYP2C19 variations may be related to cardiovascular events due to acetylsalicylic acid resistance.

BACKGROUND: In some stent implanted patients, cardiovascular events (CE) may occur. Acetylsalicylic acid (ASA) is routinely administered to these patients in order to prevent the occurrence of CE. CE may be related to gene variations which cause ASA resistance (AR). Therefore, it was aimed to investigate the relationship between COX-1, COX-2, CYP2C9 and CYP2C19 variations with CE due to AR. MATERIALS AND RESULTS: Seventy-four stent implanted patients, using 100 mg of ASA per day during five years were enrolled into the study. Following stent implantation, thirty-eight patients who had a CE within five years due to AR and 36 patients without CE were enrolled in patient and control group, respectively. AR was confirmed by platelet aggregation testing. After DNA isolation from blood; COX-1, COX-2, CYP2C19 and CYP2C9 variations were investigated with real-time polymerase chain reaction. At the end of this study, heterozygous genotype of COX-1 was found statistically high in patients whereas heterozygous genotype of CYP2C19*17 was found statistically high in controls. The presence of C and G allele in COX-1 and COX-2 were found statistically high in patients, respectively. The presence of T allele in CYP2C19*17 was found statistically high in controls. Heterozygous genotype of COX-1 variation was found statistically high in patients who have AR. Additionally heterozygous genotype of CYP2C19*17 was found statistically high in patients who have low thrombosis risk. CONCLUSIONS: COX-1 and COX-2 gene mutations may increase the risk of CE due to AR whereas CYP2C19*17 may have a protective effect in this process.

ε2 , ε3 , and ε4 variants of ApoE; rs2228570 (VDR), rs4588 and rs7041 (VDBP) polymorphisms in patients with multiple sclerosis: A case-control study in Turkish population.

AIM OF THE STUDY: Multiple sclerosis (MS) is a degenerative disease characterized by autoimmune demyelination in the central nervous system. Yet, underlined genetics or environmental markers are still controversial. The impact of vitamin D and cholesterol on disease activity has been phrased by many studies; however, the data available for the Turkish population are very limited. This study aimed to investigate the effect of vitamin D-related polymorphisms (VDBP and VDR) and cholesterol-related variants of ApoE on Turkish MS patients. MATERIALS AND METHODS: Total DNAs were extracted from peripheral blood samples of 51 MS patients and 50 healthy volunteers. rs4588 and rs7041 polymorphisms of VDBP, rs2228570 of VDR, as well as ε2, ε3, and ε4 variants of ApoE, were investigated by RT-PCR. Biochemical parameters which thought to be associated with MS were also measured. Results were evaluated statistically. RESULTS: Homozygous mutant genotype and G allele of rs2228570 in VDR, as well as heterozygous genotype of rs4588 in VDBP, were found statistically high in patients. Total cholesterol, triglyceride, and LDL-C levels were found significantly high, whereas HDL-C and vitamin D levels were low in patients. An association was found between rs4588 variation and high triglyceride levels. Similar correlations were found between ε2 genotype and low LDL-C level; ε3 genotype and higher LDL-C. Gender, triglyceride, HDL-C, and AA genotype in rs4588 had a significant effect on MS progression. CONCLUSION: The variations of rs2228570 and rs4588, vitamin D deficiency, and biological parameters related to cholesterol metabolism may be associated with MS risk.

CD4+ and CD25+ T-cell response to short-time interferon-beta therapy on IL10, IL23A and FOXP3 genes in multiple sclerosis patients.

AIM OF THE STUDY: Interferon-beta (IFN-ß), multiple sclerosis (MS) drug for years, does not have therapeutic effects on each patient. Yet, a considerable portion has experienced no therapeutic response to IFN-ß. Therefore, it is necessary to determine disease-specific biomarkers that affect drug response. Here, we aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A), as well as forkhead box P3 (FOXP3) genes on MS after IFN-ß therapy. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 42 MS patients were isolated to obtain CD4+ and CD25+ T cells. Both cell types were characterised by flow cytometry. To determine optimum drug concentration of IFN-ß, cytotoxicity assays were assessed on each cell type for 4, 16, 24 and 48 hours respectively. Then, cells were cultured in the presence of 500 IU/mL of IFN-ß. cDNA synthesis was performed after mRNA extraction. RT-PCR was performed to measure gene expressions of IL10, IL23A and FOXP3. Results were evaluated statistically. RESULTS: It was found that the cytotoxic effect of IFN-ß was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-ß. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48 hours in CD4+ T cells. For CD25+ T cells, the graded increase in FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake. CONCLUSION: Although a considerable change in expression was obtained, the long-term IFN-ß effect on both genes and cells should be determined by follow-up at least a year.