Osteopontin Gene Polymorphisms rs1126616 C>T and rs1126772 A>G are Associated with Atopic Dermatitis in Polish Population.

PURPOSE: Atopic dermatitis (AD) is a chronic, relapsing inflammatory disease, caused by environmental and genetic factors, which lead to immunological abnormalities. Osteopontin (OPN), also named secreted phosphoprotein 1 (SPP1), is a protein involved in the pathogenesis of numerous autoimmune and inflammatory conditions. However, its role in AD has not been fully elucidated. Therefore, we aim to gain an insight into the role of OPN in AD pathogenesis through investigating its gene single nucleotide polymorphisms (SNPs) and their possible associations with disease clinical features. PATIENTS AND METHODS: A total of 182 Caucasian participants (45 AD patients and 137 gender- and age-matched controls) were studied. Genomic DNA was isolated from peripheral blood samples. Genotyping for the rs1126616 C>T, rs1126772 A>G, rs9138 A>C, and rs3841116 T>G SNPs was performed by real time polymerase chain reaction (RT-PCR). RESULTS: The frequency of the minor TT genotype and the T allele of rs1126616 C>T was higher in AD patients compared to controls (P = 0.019, OD = 4.86, 95% CI = 1.46-16.20, and P = 0.047, OR = 1.77, 95% CI = 1.04-3.00, respectively) and was associated with the higher prevalence of asthma (P = 0.017, OR = 3.73, 95% CI = 0.71-19.67, and P = 0.004, OR = 3.96, 95% CI = 1.53-10.25, respectively). Likewise, the minor GG genotype and the G allele of rs1126772 A>G were more frequent in AD patients (P = 0.026, OR = 3.27, 95% CI = 1.29-8.33, and P = 0.013, OR = 1.94, 95% CI = 1.18-3.21, respectively) and were associated with the increased incidence of asthma (P = 0.016, OR = 5.06, 95% CI = 1.14-22.49, and P = 0.002, OR = 4.40, 95% CI = 1.71-11.35, respectively). Furthermore, haplotype frequency estimation determined the four-loci haplotype TGCT, as a significant risk factor for AD compared to controls (P = 0.031, OR = 9.48, 95% CI = 1.23-71.91). CONCLUSION: Our results suggest that the variation in the OPN gene might be associated with AD and increased incidence of asthma in Caucasians. Further studies should be conducted to look into the possible role of OPN as a biomarker for AD.

The preliminary association study of osteopontin 707 C/T polymorphism with systemic lupus erythematosus in a Polish population.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by genetic, environmental, and still unknown factors which lead to deregulation of the immune system. Osteopontin (OPN) is a multifunctional glycoprotein, expressed in various cell types, and found to play key roles in immunity. OPN and variants of the OPN gene are involved in inflammatory conditions, however, their role in SLE are controversial. AIM: To investigate the frequency of single nucleotide polymorphism (SNP) rs1126616 (707 C/T) variants in the OPN gene and its associations with SLE manifestations in Polish patients. MATERIAL AND METHODS: The study population consisted of 83 SLE patients and 100 gender-, age- and ethnically matched healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The association between clinical features of SLE and 707 C/T genotypes was determined. RESULTS: The mutant (CT, TT) genotypes were observed more frequently than the wild-type (CC) genotype in SLE patients compared to controls (p = 0.037). However, no association between 707 C/T variants and SLE clinical manifestations or laboratory parameters was found. CONCLUSIONS: The present data suggest that CT and TT genotypes of OPN 707 C/T SNP are associated with a higher SLE risk, but do not affect the clinical course of the disease in the Polish population.

Vitamin D-binding protein as a biomarker to confirm specific clinical diagnoses.

Introduction: Vitamin D-binding protein (DBP) performs a variety of functions as a transporter for various ligands and takes part in a number of systemic and local physiological and pathological processes. The knowledge about the pathomechanisms of this protein involvement justifies its use as a biomarker to confirm specific clinical diagnoses suggested by nonspecific signs and symptoms.Areas covered: DBP has properties of both systemic laboratory parameters measured in the blood plasma and specific parameters measured in variety of physiological fluids to assess local changes in specific body organs. Articles published in English between 1993 and 2019 were searched for in PubMed using terms DBP, vitamin D, and metabolites, inflammation. DBP is a transport protein and a regulator of immune and inflammatory processes.Expert opinion: DBP capacity for transporting numerous ligands and co-involvement of DBP in immune and inflammatory processes suggest that DBP may be used in laboratory diagnostics as a specific parameter to confirm pathomechanisms of several systemic diseases and local conditions. Changes in the concentration of DBP present in a variety of clinical material may provide valuable information for use in assessing the severity and treatment of pathological processes.

Vitamin D Toxicity-A Clinical Perspective.

Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration are the most often noted clinical symptoms of vitamin D toxicity (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its clinical manifestation, severe hypercalcemia, are related to excessive long-term intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of coincident disease that produces the active vitamin D metabolite locally. Although VDT is rare, the health effects can be serious if it is not promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT exist. Exogenous VDT is usually caused by the inadvertent or improper intake of extremely high doses of pharmacological preparations of vitamin D and is associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing. Endogenous VDT may develop from excessive production of an active vitamin D metabolite - 1,25(OH)2D in granulomatous disorders and in some lymphomas or from the reduced degradation of that metabolite in idiopathic infantile hypercalcemia. Endogenous VDT may also develop from an excessive production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams-Beuren syndrome. Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe. That phenomenon, called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism. Researchers have proposed many processes to explain VDT. Those processes include elevated activity of 1α-hydroxylase or inhibited activity of 24-hydroxylase, both leading to increased concentration of 1,25(OH)D; increased number of vitamin D receptors; and saturation of the capacity of vitamin D binding protein. Increased public awareness of vitamin D-related health benefits might increase the risk of VDT due to self-administration of vitamin D in doses higher then recommended for age and body weight or even higher than the established upper limit intake values. Consequently, the incidence of hypercalcemia due to hypervitaminosis D might increase.

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland-Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update.

INTRODUCTION: Vitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency. METHODS: A systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation system describing the strength of the recommendation and the quality of supporting evidence. Twenty-seven contributors representing different areas of expertise and medical specialties, including pediatricians, geriatricians, endocrinologists, epidemiologists, nephrologists, gynecologists and obstetricians evaluated the available published evidence related to vitamin D, formulated the goals of this document and developed a common consolidated position. The consensus group, representing six national specialist consultants and eight Polish and international scientific organizations/societies, participated in the process of grading evidence and drawing up the general and specific recommendations. RESULTS: The updated recommendations define the diagnostic criteria for the evaluation of vitamin D status and describe the prevention and treatment strategies of vitamin D deficiency in the general population and in groups at increased risk of the deficiency. Age- and weight-specific recommendations for prevention, supplementation and treatment of vitamin D deficiency are presented, and detailed practice guidance is discussed regarding the management in primary and specialized health care. CONCLUSION: Vitamin D deficiency remains still highly prevalent in Poland, in all age groups. Currently, there is a great necessity to implement a regular supplementation with recommended doses and to develop an effective strategy to alleviate vitamin D deficiency in the population. These updated recommendations are addressed to health professionals and the authorities pursuing comprehensive health policies and should also be included in public health programs aimed at preventing a broad spectrum of chronic diseases.

Vitamin D supplementation guidelines.

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.

The usefulness of monitored therapy using Clozapine concentration in the blood serum for determining drug dose in Polish schizophrenic patients.

BACKGROUND: The aim of the study is to evaluate the advisability of systematic monitoring of clozapine (CLO) concentration in serum during treatment of schizophrenia in Polish psychiatric patients. METHOD: The concentration of CLO and its metabolites: norclozapine (NCLO) and clozapine N-oxide (CLO-NO) in serum obtained from 107 patients suffering from schizophrenia was determined by high performance liquid chromatography (HPLC) method. There were two groups of patients. In the first group of patients (n=95) the concentration of drug and its metabolites was determined by one-time testing. Correlations were tested using the test statistics. In the second group of patients (n=12), 51 samples of serum were provided by the same patient in different time spans (from 6days to 14 months after the beginning of the treatment). RESULTS: Concentrations of CLO and its metabolites in blood serum do not always show a linear dependence on the applied dose for individual patients. CONCLUSION: The high volatility of CLO concentrations in blood serum of patients treated with identical doses of the drug confirmed the validity of the monitored therapy.

Determination of the stereoisomers in aqueous medium and serum and validation studies of racemic aminoalkanol derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, potential new anticancer drugs, by capillary electrophoresis.

A new method for the determination of the stereoisomers, in aqueous medium and serum, of the racemic aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which were found in earlier studies to be potential anticancer drugs, was developed and validated. The optimized conditions included 25 mM phosphate buffer adjusted to pH 2.5, containing γ-cyclodextrin at a concentration of 5% m/v, as background electrolyte, an applied voltage of +10 kV, and a temperature of 25°C. Separations were carried out using a fused-silica capillary. The developed method of determining the enantiomers of compounds I(S), I(R) and II(S), II(R) was characterized by the following parameters: a detection time within 10.8 min, a detection limit in the range of 141.2-141.7 ng/mL using the UV absorption detection at 200 nm. Good linearity (R(2) = 0.9989-0.9998) was achieved within the range of concentrations studied. A very good extraction yield of 95.4-99.7% was achieved, and recoveries were carried out from both aqueous solutions and matrix serum. The repeatability of the method for peak areas with an accuracy of the determined concentrations of the analytes in the range of 1.43-1.89%, and limits of quantitation in the range of 432.4-436.3 ng/mL were achieved.

Toll-Like Receptor 4 Gene Polymorphism C1196T in Polish Women with Postmenopausal Osteoporosis - Preliminary Investigation.

BACKGROUND: Postmenopausal osteoporosis is a systemic bone disease characterized by low bone mass after menopause. Bone remodeling is regulated by a number of factors, including the immune system. Toll-like receptors 4 (TLR4) are expressed on bone cells and modify the immune response. TLR4 gene polymorphism may take part in the development of chronic inflammation in women after menopause, which is the cause of severe bone resorption. OBJECTIVES: To examine the frequency of TLR4 C1196T genotypes in postmenopausal osteoporotic and non-osteoporotic Polish women and to investigate the possible relationship between C1196T polymorphism, bone mineral density (BMD) and the incidence of osteoporotic fractures in this group of patients. MATERIAL AND METHODS: The study involved 40 postmenopausal women with osteoporosis and 63 healthy postmenopausal non-osteoporotic women. BMD measurements were performed by dual-energy X-ray absorptiometry. DNA was extracted from peripheral blood. Genotyping was performed by real-time PCR using LightSNiP tests with SimpleProbe probes. Melting curve analysis of PCR amplicons enabled the identification of individual C1196T genotypes. RESULTS: C1196T genotype frequencies in the osteoporotic group were 88% for CC and 12% for CT. In the control group, respectively 86% and 14%. We did not observe the TT genotype. There was no association of C1196T genotypes and BMD nor the incidence of fractures but there was a correlation between genotypes and body height (p=0.035, r=0.415). Homozygous subjects for the C-allele had a lower body height with respect to heterozygous subjects. CONCLUSIONS: It is unlikely that TLR4 C1196T polymorphism is related to bone mineral density and fracture incidence in Polish osteoporotic women after menopause. However, our data suggests that the C allele may be associated with lower body height in this group. Due to the small number of participants, our observations should be considered as preliminary. Larger studies are needed to confirm our findings.

Viabilidade da mensuração de marcadores de remodelação óssea em mulheres com lúpus eritematoso sistêmico / Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus

Objetivo: Investigar a viabilidade dos marcadores de remodelação óssea (MRO) na avaliação do metabolismo ósseo em pacientes com lúpus eritematoso sistêmico (LES), de acordo com as diretrizes da International Osteoporosis Foundation e da International Federation of Clinical Chemistry and Laboratory Medicine. Métodos: O estudo incluiu 43 pacientes do sexo feminino com LES. Foram medidos os níveis séricos de propeptídeo N-terminal do procolágeno tipo I (PINP), telopeptídeo C-terminal do colágeno tipo I (CTX), osteocalcina, HPT, 25(OH)D, anticorpos anticardiolipina, antidsDNA e antinucleossomo. Resultados: Os níveis de PINP e CTX estavam elevados em pacientes com LES com idade > 45, em comparação com aqueles com idade < 45 anos, embora com significância estatística limítrofe (p = 0,05). Foram encontradas correlações entre os MRO: a mais forte foi entre o PINP e a osteocalcina (τ = 0,69, p < 0,05). Encontrou-se que o PINP e a osteocalcina estão correlacionados com o HPT (τ = 0,3, τ = 0,29, respectivamente, p < 0,05). A idade estava correlacionada com o PINP (τ = 0,23, p < 0,05). Valores elevados de PINP foram encontrados em maior frequência do que valores elevados de osteocalcina ou CTX, tanto em pacientes com idade < 45 (p = 0,001) quanto > 45 (p < 0,001). Não houve diferença estatisticamente significativa nos níveis de PINP, osteocalcina ou CTX com relação à estação do ano, nem em todo o grupo de pacientes com LES, nem naqueles com mais ou menos de 45 anos. O uso prévio de glucocorticoides não esteve associado a diferenças nos MRO. Conclusões: O aumento nos MRO no LES parece refletir predominantemente o padrão de remodelação óssea relacionado com a idade. Pode-se esperar que o PINP aumentado seja o desfecho mais comumente encontrado entre os MRO. É necessário incluir melhores diagnósticos de distúrbios ósseos com MRO, feitos de acordo com as normas internacionais de referência, na abordagem de ...

Objective: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. Methods: The study included 43 female SLE patients. Serum pro-collagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. Results: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ= 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ= 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Conclusions: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. .

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. METHODS: The study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. RESULTS: PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged < 45, although with borderline significance (p = 0.05, respectively). Correlations were found between BTMs: the strongest being between PINP and osteocalcin (τ = 0.69, p < 0.05). PINP and osteocalcin were found to be associated with PTH (τ = 0.3, τ = 0.29, respectively, p < 0.05). Age correlated with PINP (τ = 0.23, p < 0.05). Elevated PINP was found more frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p = 0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. CONCLUSIONS: Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment.

Capillary electrophoresis separation of aminoalkanol derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5,10-trione as potential anticancer drugs.

The purpose of this study, the direct separation of aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which was found in earlier studies as potential anticancer drugs, were performed. Capillary electrophoresis offers the possibility of fast, cheap, and reproducible separations for compounds I and II. In this paper, the simultaneous separation of I and II by capillary zone electrophoresis has been achieved within 8 min by use of 50 mM phosphate buffer of pH 2.5. Analysis of the two compounds in the serum plasma standards was conducted. Limits of detection of I and II by UV absorbance at 200 nm were achieved in the range of 156.3-156.6 ng/mL. The method was validated for linearity, accuracy, precision, limits of detection, and quantification. The calibration equation revealed a good linear relationship (r(2) = 0.998-0.999). Sufficient recovery was observed in the range of 96.3-99.5%. The method showed good reproducibility with intra- and interday precision of 0.97 and 1.76%, respectively. The quantification limits for the compounds were in the range of 477.0-479.8 ng/mL. The proposed method was applied to the analysis of real serum samples.

Association between Fok I vitamin D receptor gene (VDR) polymorphism and impulsivity in alcohol-dependent patients.

Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency.

INTRODUCTION: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency. METHODS: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops. RESULTS: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed. CONCLUSIONS: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.

Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus Erythematosus.

The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (r = 0.438; P = 0.002). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy.

Vitamin D and the central nervous system.

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

Serotonin 2A receptor gene (HTR2A) polymorphism in alcohol-dependent patients.

BACKGROUND: The serotonergic (5-HT) dysfunction has been frequently described in subjects with alcohol dependence (AD). In the present study, a potential relationship between T102C polymorphism in the 5-HT receptor subtype 2Agene (HTR2A) and alcohol dependence was examined. METHODS: Genotypes were analyzed in 150 AD patients diagnosed with DSM-IV criteria and in 80 healthy controls. RESULTS: The genetic analysis showed that the frequency of 102C allele and C102C genotype in AD subjects was significantly higher than in controls. Moreover, AD patients homozygous for C allele had significantly lower age at onset of alcohol problems than subjects having at least one T allele. CONCLUSION: The results suggest a potential role of the T102C HTR2A polymorphism in development of alcohol dependence.

The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients.

High levels of impulsivity can increase the vulnerability for development of alcohol dependence. Moreover, impulsivity is considered to be a predictor of poor treatment outcomes. Few studies, however, have directly examined the genetics of impulsivity in alcohol-dependent patients. We analyzed the relationships between a well-recognized genetic marker of serotonin activity and levels of impulsivity as measured by both the Barratt Impulsiveness Scale (BIS-11) and the stop-signal task among 304 alcohol-dependent patients. The stop-signal task was used as an independent, objective method of estimating the level of behavioral impulsivity, and the BIS-11 as a self-report measure of global impulsivity. Blood was collected and analyzed for the T102C (rs6313) polymorphism in the serotonin type 2A receptor gene (HTR2A). Our results indicate a significant association between high levels of behavioral impulsivity and the C/C genotype of rs6313 in alcohol-dependent patients. The CC genotype has been previously found to be associated with a reduction in 5HT2A receptors in the central nervous system. These results support the hypothesis that genetic factors are important determinants of behavioral impulsivity in alcohol-dependent patients, and that the serotonin system plays an important role in establishing its level.

Vitamin D supplementation and status in infants: a prospective cohort observational study.

OBJECTIVE: Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants. PATIENTS AND METHODS: One hundred thirty-four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25-hydroxyvitamin D (25-OHD) serum concentration at the 6th and 12th months were assessed. RESULTS: Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25-OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25-OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25-OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25-OHD concentration change between the 6th and the 12th months negatively correlated with the 25-OHD level assessed at the 6th month (r = -0.82; P < 0.0001). CONCLUSIONS: Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.