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.

Different VDR, VDBP genotypes and vitamin D levels may effect obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent disorder which results in markedly reduced (hypopnea) or absent (apnea) airflow at the nose/mouth. Since vitamin D deficiency has found in an association with some disorders it is thought to be related with OSAS progression. The aim of this study is to investigate the association between VDR, VDBP mutations, vitamin D level and some environmental risk factors with OSAS. Fifty individuals who were diagnosed as OSAS were selected as patients, 50 healthy volunteers without any disease were selected as controls. FokI (rs2228570) and BsmI (rs1544410) mutations in VDR; rs4588 and rs7041 mutations in VDBP were investigated with quantitative real-time polymerase chain reaction (qPCR). Other risk factors were also investigated. Results were evaluated statistically. Statistically significant differences were observed according to the baseline characteristics between the groups, When groups were compared with each other, CA genotype in rs4588, CC genotype in rs2228570 and AA genotype in rs1544410 mutations were found statistically significant in patients whereas TC genotype in rs2228570 and GA genotype in rs1544410 mutations were found statistically significant in controls. When the relation between risk factors and genotypes were investigated, statistically significant associations were detected for body mass index (BMI), waist circumference, Apnea-Hypopnea Index (AHI), excessive daytime sleepiness (EDS), vitamin D and triglyceride levels. VDR and VDBP mutations were found highly related with OSAS. Possible tracking of these mutations and risk factors may help to understand the metabolism as well as the progression of the disease.

VDBP, VDR Mutations and Other Factors Related With Vitamin D Metabolism May Be Associated With Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is an insulin dependent autoimmune disorder resulting the progressive destruction of pancreatic beta cells. Another possible factor considered to be related with T1DM is vitamin D deficiency. Therefore in this study it was aimed to investigate the associations between T1DM, vitamin D binding protein (VDBP) and vitamin D receptor (VDR) gene mutations which are related with vitamin D metabolism. Fifty five T1DM paitents and 40 healthy volunteers were recruited to the study. FokI (rs2228570), BsmI (rs1544410) mutations in VDR; rs4588 and rs7041 polymorphisms in VDBP were investigated with real-time polymerase chain reaction (RT-PCR). Other risk factors related with T1DM were also investigated. Results were evaluated statistically. Statistically significant relations were found in glucose, HbA1c, TSH, higher 25[OH]D, free vitamin D, calcium, albumin, log25[OH]D, retinopathy, higher than 30 mg/day microalbuminuria in T1DM patients. Also statistically significant association was found between C allele in Fok1 and T1DM in patients. When the relation between the risk factors and mutations were investigated, it was found that VDBP, free vitamin D and bioactive vitamin D were significantly associated with rs7041 mutation in VDBP whereas HDL was significantly associated with rs2228570 mutation in VDR. Other studies with larger data sets may demonstrate more reliable statistical results to rule out genotype-phenotype correlations of the disease.