The Oncogenic PI3K-Induced Transcriptomic Landscape Reveals Key Functions in Splicing and Gene Expression Regulation.

The phosphoinositide 3-kinase (PI3K) pathway regulates proliferation, survival, and metabolism and is frequently activated across human cancers. A comprehensive elucidation of how this signaling pathway controls transcriptional and cotranscriptional processes could provide new insights into the key functions of PI3K signaling in cancer. Here, we undertook a transcriptomic approach to investigate genome-wide gene expression and transcription factor activity changes, as well as splicing and isoform usage dynamics, downstream of PI3K. These analyses uncovered widespread alternatively spliced isoforms linked to proliferation, metabolism, and splicing in PIK3CA-mutant cells, which were reversed by inhibition of PI3Kα. Analysis of paired tumor biopsies from patients with PIK3CA-mutated breast cancer undergoing treatment with PI3Kα inhibitors identified widespread splicing alterations that affect specific isoforms in common with the preclinical models, and these alterations, namely PTK2/FRNK and AFMID isoforms, were validated as functional drivers of cancer cell growth or migration. Mechanistically, isoform-specific splicing factors mediated PI3K-dependent RNA splicing. Treatment with splicing inhibitors rendered breast cancer cells more sensitive to the PI3Kα inhibitor alpelisib, resulting in greater growth inhibition than alpelisib alone. This study provides the first comprehensive analysis of widespread splicing alterations driven by oncogenic PI3K in breast cancer. The atlas of PI3K-mediated splicing programs establishes a key role for the PI3K pathway in regulating splicing, opening new avenues for exploiting PI3K signaling as a therapeutic vulnerability in breast cancer. SIGNIFICANCE: Transcriptomic analysis reveals a key role for the PI3K pathway in regulating RNA splicing, uncovering new mechanisms by which PI3K regulates proliferation and metabolism in breast cancer. See related commentary by Claridge and Hopkins, p. 2216.

Enhanced Performance of ΔTad upon Frequent Alternating Magnetic Fields in FeRh Alloys by Introducing Second Phases.

The cyclability and frequency dependence of the adiabatic temperature change (ΔTad) under an alternating magnetic field (AMF) are significantly important from the viewpoint of refrigeration application. Our studies demonstrated, by direct measurements, that the cyclability and low-magnetic-field performance of ΔTad in FeRh alloys can be largely enhanced by introducing second phases. The ΔTad under a 1.8 T, 0.13 Hz AMF is reduced by 14%, which is much better than that (40-50%) of monophase FeRh previously reported. More importantly, the introduction of second phases enables the antiferromagnetic-ferromagnetic phase transition to be driven by a lower magnetic field. Thus, ΔTad is significantly enhanced under a 0.62 T, 1 Hz AMF, and its value is 70% larger than that of monophase FeRh previously reported. Although frequency dependence of ΔTad occurs, the specific cooling power largely increases by 11 times from 0.17 to 1.9 W/g, as the frequency increases from 1 to 18.4 Hz under an AMF of 0.62 T. Our analysis of the phase transition dynamics based on magnetic relaxation measurements indicates that the activation energy barrier is lowered owing to the existence of second phases in FeRh alloys, which should be responsible for the reduction of the driving field. This work provides an effective way to enhance the cyclability and low-magnetic-field performance of ΔTad under an AMF in FeRh alloys by introducing second phases.

Bosnian Study on Markers of Ischaemic Stroke in Adults 20-50 Years Old (SMISAO): Preliminary Report.

Previous research suggested that several genetic polymorphisms are associated with increased risk of ischaemic stroke (IS) in young adults. However, the predictive biomarkers of IS in young adults are still unclear. Our aim was to assess the contribution of modifiable and genetic factors in IS in young adults. In total, 40 stroke patients and 40 healthy controls aged 20 to 50 years were recruited. Data on modifiable factors were collected, then participants were genotyped for seven SNPs linked to thrombophilia: ACE rs1799752, PAI-1 rs1799889, APOE rs1412 and rs429358, FV rs6025 and rs1800595, and FII rs62623459. Significantly increased risk factors: hypertension and dyslipidaemia in stroke patients compared with the controls: 50.0 % vs 27.5 % and 75.0 % vs 40.0% (P = 0.039 and P = 0.002, respectively) were observed. Stroke patients compared with controls did not differ in distribution of ACE, APOE, FV, and FII variants. The 4G4G homozygotes of the PAI-1 gene were significantly more prevalent in stroke patients compared to the controls: 42.5 % vs 17.5 %, (P = 0.033). In the group with the small vessel occlusion subtype of stroke, statistically significant overrepresentation of 4G4G homozygotes and frequency of the 4G allele compared with controls: 57.1 % vs 17.5 % and 0.7 vs 0.45 (P = 0.026 and P = 0.03, respectively) were observed. Independent predictors of stroke incident were: dyslipidaemia (OR (95% CI) = 4.2 (1.4-12.4)) and 4G4G genotype (OR (95% CI) = 3.9 (1.1-13.7)). These results confirm the contribution of dyslipidaemia and 4G4G genotype in the increased risk of IS in young Bosnian adults.

Influência do sistema de criação em piso sobre cama e gaiola sobre as características ósseas e a qualidade físico-química e microbiológica de ovos de galinhas / Influence of the floor and cage creation system on the bony characteristics and the physical-chemical and microbiological quality of hen eggs

O experimento foi realizado no setor de avicultura/UFRRJ, utilizando 348 galinhas semipesadas (linhagem Dekalb Brown), com 52 semanas de idade, criadas sob dois sistemas de produção: cage-free e em gaiolas. Os dados obtidos pela análise físico-química e microbiológica dos ovos e a resistência óssea à quebra foram submetidos à análise de variância. No caso de ocorrerem efeitos dos diferentes sistemas de produção, foi aplicado o teste de Tukey a 5% de probabilidade para comparação das médias. A qualidade físico-química foi igualmente favorecida pelos dois sistemas de produção, indicando que as circunstâncias experimentais propiciaram condições adequadas para a formação de ovos de boa qualidade. O sistema de gaiola não desfavoreceu as características ósseas das galinhas, apontando que, em densidades adequadas, a gaiola pode não exercer um fator prejudicial para a qualidade óssea. O sistema de produção cage-free piorou a contaminação da casca, comprovando que ovos postos em ninhos são mais contaminados em comparação aos produzidos em gaiolas.(AU)

The experiment was carried out in the poultry sector / UFRRJ, using 348 semi-heavy hens (Dekalb Brown line), 52 weeks old, raised under two cage-free production systems and cages. The data obtained by the physical-chemical and microbiological analysis of the eggs and the bone resistance to the break were submitted to analysis of variance, in case of effects of the different production systems, the Tukey's test was applied at 5% of probability for comparison of the means. The physical-chemical quality was also favored by the two production systems, indicating that the experimental circumstances provided adequate conditions for the formation of good quality eggs. The cage system did not disfavor the bony characteristics of the hens, indicating that at suitable densities, the cage may not exert a detrimental factor to bone quality. The cage-free production system worsened shell contamination by proving that nesting eggs are more contaminated compared to those produced in cages.(AU)

First Bosnian Study of the Relationship between APOE rs7412 and rs429358 Variants and Pregnancy Loss.

Due to inconsistent results of APOE variants in the survival of pregnancy we investigated the potential relationship of APOE rs7412 and rs429358 with pregnancy loss (PL) in Bosnian women. We enrolled 154 women with PL. The minimum week of miscarriage was 6, while the maximum was 28. As a control group, an equal number of mothers with at least one live-born child was included. All women were recruited from the Institution of Health Protection of Women and Motherhood in Sarajevo, Bosnia and Herzegovina. Genotyping was performed by real- time PCR at the Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University. The prevalence of genotypes E2/E3, E2/E4, E3/E3, E3/E4, E4/E4 in the group with and without PL were: 14.3 %, 1.3 %, 70.8 %, 12.3 %, 1.3 %, and 13.6 %, 1.3 %, 70.1 %, 14.3 %, 0.7 %, respectively. The frequency of the E4/E4 genotype in women with 1-2 and 3-4 PL compared to women without PL did not differ significantly between those three groups (P value = 0.0712). The frequencies of alleles ԑ2, ԑ3, ԑ4 in the group with and without PL were: 6.8 %, 85.1 %, 8.1 % and 7.5 %, 84.1 %, 8.4 %, respectively, and did not differ significantly. We conclude that our study does not confirm rs7412 and rs429358 as a potential risk factor for PL in the studied group. To elucidate the relationship between PL and variants of the APOE gene, studies with a larger sample size and placental histomorphology and genetic diagnosis are required.

The Lack of Association between FCN2 Gene Promoter Region Polymorphisms and Dental Caries in Polish Children.

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in the gene encoding ficolin-2 protein (FCN2 gene) at positions -986 (rs17514136), -602 (rs3124953), and -4 (rs3124952) with dental caries in Polish children. Two hundred and sixty Polish Caucasian children aged 15 years were enrolled in this study: 82 with "higher" caries experience (DMFT >5) and 178 with "lower" caries experience (DMFT ≤5). In addition, subjects with caries experience (DMFT ≥1) and caries-free subjects (DMFT = 0) were compared. FCN2 SNPs were genotyped with PCR-RFLP methods. There were no significant differences in the genotype, allele, or haplotype distributions in 3 analyzed SNPs of the FCN2 gene between children with "higher" and those with "lower" caries experience as well as between children with caries experience and caries-free children. In conclusion, we did not find any association of FCN2 promoter polymorphisms at positions -986, -602, and -4 with dental caries in Polish children.

Immune related factors in pathogenesis of autism spectrum disorders.

OBJECTIVE: Etiology of Autism Spectrum Disorders (ASD) is insufficiently known. It is suggested that genes play a crucial role in ASD but additional environmental factors to exacerbate the syndrome are needed. Recently, the inflammatory factors in ASD that may predispose to the disorder attract a great attention. Therefore, the aim of this article was to review the literature on the possible association of the immune system malfunctions with the risk of developing ASD. MATERIALS AND METHODS: Available articles from PubMed and Google Scholar were analyzed using time descriptors: 1996-2015 and key words: autism spectrum disorder, cytokines and immune system. RESULTS: Individuals with ASD demonstrate aberrant immune response in central nervous system, peripheral blood and gastrointestinal tract. CONCLUSIONS: Immune malfunctions may play a role in developing ASD.

[Influence of Selected Reproductive Factors and Smoking on Age at Menopause]. / Einfluss ausgewählter Reproduktionsfaktoren sowie des Rauchens auf das Alter bei Eintreten der Menopause.

Introduction: Early menopause may be associated with serious health risks resulting from, for example, decreased oestrogen levels. This may occur despite hormone replacement therapy. Aim: The aim of this study was the determination of the effect of selected reproductive factors and smoking on age at the onset of menopause in women from Szczecin and surrounding areas. Material and Methods: 305 women after natural menopause were asked to complete a questionnaire, and blood samples were collected from them to test for the levels of follicle stimulating hormone (FSH) and oestradiol (E2). Results: Smoking women experienced menopause on average more than a year earlier than non-smokers, but this difference was not statistically significant. There was no statistically significant effect of age at menarche or first birth on age at the last menstrual period. Conclusions: Age at menarche and first birth were not related to age at menopause. In smoking women, menopause occurred earlier but the difference was not statistically significant.

Phosducin regulates secretory activity in TT line of thyroid parafollicular C cells.

The endocrine activity of the thyroid gland is accomplished by its follicular and parafollicular cells. In these cells, numerous G proteins-dependent pathways are active and potentially could be regulated by a 33-kDa cytoplasmic protein phosducin, which interacts with the Gß subunit and may compete with Gα or Gßγ dimer effectors. Significant expression of phosducin has been shown in the retina, pineal gland, and some neurons. Here, we studied postoperative thyroid tissue samples collected from patients with nodular goiter and 2 thyroid-derived cell lines for the presence of phosducin. Using reverse transcription PCR with product sequencing and highly sensitive immunodetection we identified phosducin mRNA and protein in the thyroid gland and parafollicular C TT cells, but not in the follicular Nthy-ori 3-1 cell line. We also observed that siRNA-mediated silencing of phosducin gene expression decreased Ca(2+)-stimulated secretion of calcitonin and serotonin by TT cells.

Complex refractive indices in the near-ultraviolet spectral region of biogenic secondary organic aerosol aged with ammonia.

Atmospheric absorption by brown carbon aerosol may play an important role in global radiative forcing. Brown carbon arises from both primary and secondary sources, but the mechanisms and reactions of the latter are highly uncertain. One proposed mechanism is the reaction of ammonia or amino acids with carbonyl products in secondary organic aerosol (SOA). We generated SOA in situ by reacting biogenic alkenes (α-pinene, limonene, and α-humulene) with excess ozone, humidifying the resulting aerosol, and reacting the humidified aerosol with gaseous ammonia. We determined the complex refractive indices (RI) in the 360-420 nm range for these aerosols using broadband cavity enhanced spectroscopy (BBCES). The average real part (n) of the measured spectral range of the NH3-aged α-pinene SOA increased from n = 1.50 (±0.01) for the unreacted SOA to n = 1.57 (±0.01) after 1.5 h of exposure to 1.9 ppm NH3, whereas the imaginary component (k) remained below k < 0.001((+0.002)(-0.001)). For the limonene and α-humulene SOA the real part did not change significantly, and we observed a small change in the imaginary component of the RI. The imaginary component increased from k = 0.000 to an average k = 0.029 (±0.021) for α-humulene SOA, and from k < 0.001((+0.002)(-0.001)) to an average k = 0.032 (±0.019) for limonene SOA after 1.5 h of exposure to 1.3 and 1.9 ppm of NH3, respectively. Collected filter samples of the aged and unreacted α-pinene SOA and limonene SOA were analyzed off-line by nanospray desorption electrospray ionization high resolution mass spectrometry (nano-DESI/HR-MS), and in situ using a Time-of-Flight Aerosol Mass Spectrometer (ToF-AMS), confirming that the SOA reacted and that various nitrogen-containing reaction products formed. If we assume that NH3 aging reactions scale linearly with time and concentration, which will not necessarily be the case in the atmosphere, then a 1.5 h reaction with 1 ppm NH3 in the laboratory is equivalent to 24 h reaction with 63 ppbv NH3, indicating that the observed aerosol absorption will be limited to atmospheric regions with high NH3 concentrations.

The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer's disease under daily practice conditions.

BACKGROUND: Rivastigmine is the only cholinesterase inhibitor (ChEI) available as transdermal patch. The patch was developed to improve gastrointestinal tolerability and treatment adherence to higher dosages as compared with oral medication. Preferences of patients and caregivers for the patch were reported; however, neither patient compliance nor caregiver burden has yet been measured under routine practice conditions. METHODS: This was a prospective, multi-centre, observational study in patients with Alzheimer's disease treated with rivastigmine patch in Germany. To compare the transdermal with oral dosage forms, physicians were asked to enrol patients who recently switched from oral to transdermal medication. Beyond effectiveness and tolerability, outcome measures were drug adherence evaluated by the Morisky questionnaire, and caregiver burden, measured as the daily time expenditure for dressing the patient, controlling appearance and administration of medication. RESULTS: In total, 1104 outpatients (57.5% female gender; mean age 77 ± 7 years) were enrolled in 220 sites. After 6 months of treatment, 67.5% of patients had an improved Clinical Global Impression and the Mini-Mental State Examination score increased from 19.0 ± 5.1 to 20.0 ± 5.2 (p < 0.001); 84.1% of patients were still on treatment, 64.6% on the target dose of 9.5 mg/day. Compliance and patient satisfaction with therapy continuously increased over the study period and average time savings of caregivers added up to 20 min/day. In general, tolerability was deemed good and there were no unexpected adverse events. CONCLUSIONS: Transdermal rivastigmine is an effective treatment alternative, which may improve adherence and treatment satisfaction of the patient and relieve the caregiver. Controlled parallel-group trials are warranted. CLINICAL TRIALS REGISTRATION: none (observational study).

Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity.

BACKGROUND/AIM: Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic mice. METHODS/RESULTS: Db/db mice were randomized to high sodium (HS 1.6% Na+, n = 6) or low sodium (LS 0.03% Na+, n = 8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n = 8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p < 0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p < 0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p < 0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p < 0.01). CONCLUSION: In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders.

Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects.

AIM: Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity-induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo-controlled, double-blind, randomized, parallel-group study (NCT01406015). METHODS: Thirty-two non-diabetic, obese subjects [body mass index (BMI) 30 to 45 kg/m(2) ] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation (FMD) of brachial artery and renal plasma perfusion by clearance of para-aminohippurate (PAH). RESULTS: There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p < 0.02, post-treatment vs. baseline) and urine aldosterone (11.0 ± 7 vs. 4.8 ± 2.4 µg/g creatinine; p < 0.01) and decreases in systolic blood pressure (116 ± 11 vs. 123 ± 10 mmHg; p < 0.001). There were no changes in these variables in the placebo group. Neither spironolactone nor placebo treatment had a significant effect on ISI or other indices of glucose metabolism [insulin resistance by homeostatic model assessment (HOMA), area under the curve for insulin, area under the curve for glucose], brachial artery reactivity or the renal plasma perfusion values. Changes in these variables were similar in two groups. CONCLUSIONS: We conclude that 6 weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.

ß2-adrenergic receptor gene polymorphism and response to bronchodilating treatment evaluated by spirometry.

ß2-adrenergic receptors re abundantly expressed in airways, which explains the role of ß2 agonists, the strongest bronchodilators, in treatment of bronchial constriction. There may be a relation between ß2ADR gene polymorphism and the response to treatment with ß2 agonists. In the present study we attempted to study these relationship in vivo, estimating spirometric values before and after the use of salbutamol in reference to variant of ß2ADR gene polymorphisms. The study involved 148 healthy male volunteers. After the examination of the gene polymorphism of the ß2-adrenergic receptor (ß2-ADR) at nucleotide positions 46 and 79 (g.46 and g.79) we performed spirometry testing in all subjects. The pulmonary function was checked twice a day; before and 15 min after the administration of salbutamol. All subjects had normal basic values of spirometry. The use of salbutamol significantly increased spirometric values in all groups determined by ß2ADR gene polymorphisms. Analysis of the spirometric values in individual groups showed a significant increase only in peak expiratory flow (g.46AA and g.79CC). The results of this study give an insight into a possibly important mechanism of the response to treatment with ß2-agonists.

Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake.

Serum- and glucocorticoid-inducible kinase 1 (SGK1) has a central role in epithelial sodium channel (ENaC)-dependent Na(+) transport in the distal nephron. We hypothesized that SGK1 gene variants may contribute to the effect of dietary salt intake on blood pressure (BP) in humans with hypertension, and consequentially influence renin-angiotensin-aldosterone (RAA) system activity. Our study population included 421 hypertensive Caucasian participants of the HyperPath group who had completed a dietary salt protocol with measurement of BP and RAA system activity. Three SGK1 tagging single nucleotide polymorphisms (SNPs) from the HapMap CEU population captured the genetic variation in the SGK1 region. Assuming an additive genetic model, two SNPs (rs2758151 and rs9402571) were associated with BP and plasma renin activity (PRA) effects of dietary salt intake. Major alleles were associated with higher systolic BP on high salt and decreased PRA on low salt. In contrast, low salt neutralized genotype differences. Similar, non-significant trends were observed in a normotensive population (N=152). Genotype was also associated with two salt-sensitive subtypes of hypertension. SGK1 genetic variants are associated with salt sensitivity of BP and PRA in human hypertension. Genotype status at these SGK1 variants may identify individuals prone to salt-sensitive hypertension.

Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study.

BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.

Polarization ellipse and Stokes parameters in geometric algebra.

In this paper, we use geometric algebra to describe the polarization ellipse and Stokes parameters. We show that a solution to Maxwell's equation is a product of a complex basis vector in Jackson and a linear combination of plane wave functions. We convert both the amplitudes and the wave function arguments from complex scalars to complex vectors. This conversion allows us to separate the electric field vector and the imaginary magnetic field vector, because exponentials of imaginary scalars convert vectors to imaginary vectors and vice versa, while exponentials of imaginary vectors only rotate the vector or imaginary vector they are multiplied to. We convert this expression for polarized light into two other representations: the Cartesian representation and the rotated ellipse representation. We compute the conversion relations among the representation parameters and their corresponding Stokes parameters. And finally, we propose a set of geometric relations between the electric and magnetic fields that satisfy an equation similar to the Poincaré sphere equation.

MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children.

OBJECTIVE: The aim of the study was to examine whether the MBL2 C(-290)G and G161A, MASP2 A359G, AMELX C287T and C522T, and ENAM C2452T polymorphisms are associated with dental caries. SUBJECTS AND METHODS: Genomic DNA of 95 Polish children with 'higher caries experience' (HC) and 84 subjects with 'lower caries experience' (LC) belonging to two age-groups (5 and 13 years old) was extracted from the buccal mucosa. SNPs were genotyped with PCR-RFLP methods. RESULTS: Among 5-year-old children, we found significantly higher percentage of subjects carrying MBL2 (-290)G allele in HC group compared with LC group (43.2%vs 17.6%, P = 0.023). MBL2 C(-290)G-G161A C-G haplotype was overrepresented in LC group in 5-year-olds (P = 0.01), while the opposite association was observed in 13-year-olds, where C-G was overrepresented in HC group (P = 0.028). In 5-year-old children, the frequency of MBL2 G-G haplotype was higher in HC group compared with LC subjects (P = 0.045), while the opposite association (with borderline significance) was observed in 13-year-old children (P = 0.057). SNPs in MASP2, AMELX, and ENAM were not associated with dental caries. CONCLUSION: MBL2 gene polymorphism is associated with caries experience in Polish children, but the direction of this association seems to be opposite in primary and permanent dentition.