TPH1 gene polymorphism rs211105 is associated with serotonin and tryptophan hydroxylase 1 concentrations in acute pancreatitis patients.

BACKGROUND: The role of serotonin and its metabolic pathway in proper functioning of the pancreas has not been thoroughly investigated yet in acute pancreatitis (AP) patients. Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. This study aimed to explore the association of a rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in a population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. RESULTS: Our data showed an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95 % CI 0.94-6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotypes in the control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs = - 0.415, p = 0.0018; GT: Rs = - 0.457, p = 0.0066), while for the AP group the highest levels of TPH among the TT genotype were associated with lower levels of serotonin (TT: Rs = - 0.749, p < 0.0001, and in the GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs = - 0.738, p = 0.037). CONCLUSIONS: Here, a new insight in the potential role of a selected genetic factor in pancreatitis development was shown. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important points in acute pancreatitis.

Vitamin D Binding Protein (VDBP) and Its Gene Polymorphisms-The Risk of Malignant Tumors and Other Diseases.

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half-life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases).

CYP27B1 Gene Polymorphism rs10877012 in Patients Diagnosed with Colorectal Cancer.

Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. Intestinal cells are CYP27B1 gene expression sites and, as a consequence, they are capable of converting pro-vitamin D into the active paracrine and autocrine forms. It was demonstrated that rs10877012 polymorphism in the CYP27B1 gene influenced the circulating vitamin D level. This provided a rationale for determining the role that this polymorphism plays in the risk of developing colon cancer. In this study, we investigated the association of rs10877012 (T/G) polymorphism in the CYP27B1 gene with CRC susceptibility. The study population (n = 325) included CRC patients (n = 106) and healthy controls (n = 219). DNA was extracted from peripheral leukocytes and analyzed for the CYP27B1 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We found an association between the presence of the T allele at the polymorphic site (odds ratio (OR) = 2.94; 95% CI 1.77-4.86; p < 0.0001) and a decreased CRC incidence.

Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene: The Risk of Malignant Tumors and Other Chronic Diseases.

: Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. This review presents gathered data that relate to genetic variants in CYP27B1 gene in correlation to multiple diseases, mostly concerning colorectal, prostate, breast, lung, and pancreatic cancers, as well as on other pathologies, such as non-Hodgkin's lymphoma, oral lichen planus, or multiple sclerosis.

Serum cytokine levels in children with spectrum autism disorder: Differences in pro- and anti-inflammatory balance.

BACKGROUND: Autism Spectrum Disorders (ASDs) is a developmental and neurological disorder that affects all aspects of social communication, with limited and stereotypical interest, and atypical responses to sensory stimuli. Diagnosis of ASD is currently phenotype based with no reliable laboratory test available to assist clinicians. Researches have shown that individuals with autism often exhibit dysfunction of cytokines. METHODS: A total of 42 patients with ASD and 20 matched controls participants were recruited for the study. Diagnosis was conducted by medical specialists and based on the International Classification of Mental and Behavioral Disorders - ICD-10, DSM-5 and CARS sore. Whole blood samples were collected and serum IL's and chemokin levels were made using ELISA kits. RESULTS: Results demonstrated that in comparison to the controls, the individuals with autism showed significantly higher concentration of IL-1ß, IL-4, IL-6 and IL-13. We also demonstrated significant correlations between the levels of cytokines which implies the presence of an interactive network between them. The results of ROC analysis indicated the 4-factors (IL-1ß, IL-4, IL-6 and IL-13) could be potential biomarkers in diagnosis of ASD. CONCLUSIONS: In this study, serum levels of cytokine differed among children with ASD. However, the findings of this support the possibility of using an appropriate selection of serum cytokine for the diagnosis ASD and emphasize the need to standardize quantitative methods for serum analysis.

Genetic Polymorphism of ß-Casein Gene in Polish Red Cattle-Preliminary Study of A1 and A2 Frequency in Genetic Conservation Herd.

Although there is growing interest in Red cow's milk in Poland, to date there are few reports investigating the characteristics of milk components in the studied population. Particular emphasis on milk proteins is advised, since ß-casein is a source of bioactive peptides named ß-casomorphins. ß-casomorphin 7, which originates mostly from ß-casein variants A1, may be a significant risk factor in human ischemic heart disease, arteriosclerosis, type I diabetes, sudden infant death syndrome, and autism. The aim of the present study was to identify CSN2 polymorphism gene in exon 7 using the genomic sequence from GenBank (M55158), g.8101C>A, (codon 67). Blood samples were collected from 201 Polish Red cattle (24 males and 177 females). The genotype of ß-casein was determined using PCR-ACRS. The frequency of ß-casein A2 in Polish Red population was 0.47. ß-casein A2 frequency in Polish Red bulls and in cows was 0.58 and 0.37, respectively.

A novel concept of immunological and allergy interactions in autism spectrum disorders: Molecular, anti-inflammatory effect of osthole.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by Diagnosis and Statistic Manual 5 (DSM-5) as persistent social interaction and communication deficient across multiple contexts. Various immunological findings have been reported in children with ASD, and co-existing allergic problems have been recorded in children diagnosed with ASD. Osthole, the effective component of Chinese traditional medicine, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of osthole on the histamine-induced inflammatory responses in PBMC cells. METHODS: Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (n = 29); (2) ASD group without allergy/asthma (n = 29); (3) Allergy group (n = 30) and from typically developing age-matched control subjects (n = 28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation. RESULTS: Children with ASD may show either an innate proinflammatory response or increased activity of COX-2 which could display more impaired behavioral profile than children with non-inflamed. This study indicated that COX-2 may be involved in pathogenesis of ASD and/or allergy, and osthole could be used to decrease the effects of COX-2 in inflammation and ASD development. High incidence of allergy in ASD patients may indicate immune dysregulation that could be of relevance to the pathophysiology, symptomatology or neuroimmunology of ASD. CONCLUSIONS: This study shows that fexofenadine (FXF - antihistamine drug) and osthole exhibit selective COX-2 enzyme inhibitory activity. The selective COX-2 activity of osthole may explain further the anti-inflammatory properties of osthole in relieving congestion in allergic rhinitis, and as distinctive effects between FXF and osthole were observed, individual antihistamines may have different modes of action via the COX enzyme system.

Effect of the Fexofenadine on the expression of HRH-1 and HRH-4 receptor in Peripheral Blood Mononuclear Cell isolated from children with diagnosed allergy - in vitro study Short communication.

PURPOSE: Fexofenadine (FXF) is the active metabolite of terfenadine with selective peripheral H1 receptor antagonist activity. FXF is a third-generation antihistamine, non-sedating, rapid and very long acting used in symptoms associated with allergic diseases such as allergic rhinitis, asthma and dermatitis. The pleiotropic effects of histamine are mediated by four types of receptors that belong to the G-protein-coupled receptor family: histamine H1 receptor (HRH-1), histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Our hypothesis is that HRH-4 opens new possibility in treatment in allergy diseases and FXF could be the antagonist of both HRH-1 and HRH-4. METHODS: We isolated a peripheral blood mononuclear cell (PBMC) from children with diagnosed allergies and healthy - control group and measured the HRH-1 and HRH-4 mRNA gene expression using Quantitive Real-Time PCR. We obtained the results from basal gene expression and after FXF and histamine stimulation. RESULTS: HRH-1 mRNA basal gene expression shows significantly higher, and HRH-4 shows significantly lower expression in allergy group compared to control. In both groups HRH-1 mRNA gene expression was observed as statistically significant increased after histamine stimulation compared to cells not treated, while in HRH-4 only in allergy group we observed statistical increase. FXF successively blocked histamine affinity in HRH-1 mRNA gene expression but not in HRH-4, where we not observed any reaction. CONCLUSIONS: Results clearly overturned our hypothesis about the possibility of using FXF to block over-expression HRH-4 and open new way of treatment in allergy diseases.

Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders.

Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC 3.4.14.5) and it is exogenous substrate, ß-casomorphin-7 (BCM7) in autism etiology. Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters. The inspiration for this study emanated from clinical experience of the daily diet role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.

High Expression of IL-1RI and EP2 Receptors in the IL-1ß/COX-2 Pathway, and a New Alternative to Non-Steroidal Drugs-Osthole in Inhibition COX-2.

BACKGROUND: Osthole (7-methoxy-8-isopentenylcoumarin) is natural coumarin isolated from the fruit of Cnidium monnieri (L.) Cusson, which is commonly used in medical practice of traditional Chinese medicine (TCM) in various diseases including allergies and asthma disorders. PURPOSE: Osthole was tested for the anti-histamine, anti-allergic, and inhibitory effects of COX-2 (cyclooxygenase-2) in children with diagnosed allergies. Additionally, we hypothesize that stated alterations in children with diagnosed allergies including increased expression of interleukin 1-ß receptor type 1 (IL-1 type I) and E-prostanoid (EP) 2 receptors, as well as raised expression, production, and activity of COX-2 and IL-1ß in incubated medium are approximately connected. Furthermore, we establish the mechanisms included in the changed regulation of the COX-2 pathway and determine whether osthole may be COX-2 inhibitor in peripheral blood mononuclear cells (PBMCs). METHOD: PBMCs were obtained from peripheral blood of healthy children (control, n = 28) and patients with diagnosed allergies (allergy, n = 30). Expression of the autocrine loop components regulating PGE2 production and signaling namely IL-1 type I receptor (IL-1RI), cyclooksygenaze-2 (COX-2), E-prostanoid (EP) 2, and also histamine receptor-1 (HRH-1) was assessed at baseline and after stimulation with histamine, osthole, and a mixture of histamine/osthole 1:2 (v/v). This comprised the expression of histamine receptor 1 (HRH-1), IL-1RI, COX-2, EP2 receptor, and the secretion of IL-1ß and COX-2 in cultured media and sera. RESULTS: Compared with control group, basal mRNA expression levels of HRH-1, IL-1RI, COX-2, and EP2 were higher in the allergy group. Histamine-induced EP2 and COX-2 expression mRNA levels were also increased. CONCLUSIONS: Osthole successively inhibits PGE2 and COX-2 mRNA expression. Furthermore, osthole reduces the secretion of COX-2 protein in signaling cellular mechanisms. Changed EP2 expression in children with allergies provides higher IL-1RI induction, increasing IL-1ß capacity to increase COX-2 expression. This effects in higher PGE2 production, which in turn increases its capability to induce IL-1RI.

Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene (VDR) May Have an Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations of AP Patients and Alcohol-Abuse Controls.

Vitamin D imbalance is suggested to be associated with the development of pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but not yet in pancreatitis. The aim of this study was to explore possible associations of the four SNPs in the VDR receptor gene in a population of acute pancreatitis patients and alcohol-abuse controls, and to investigate the association with acute pancreatitis (AP) susceptibility. The study population (n = 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse control group (n = 110). All patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI: 1.68⁻4.03; p < 0.0001) to be almost three times more frequent in the AP group compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in the vitamin D receptor may have an impact on the development of acute pancreatitis due to the lack of the protective role of vitamin D.

Cytokines concentrations in serum samples from allergic children-Multiple analysis to define biomarkers for better diagnosis of allergic inflammatory process.

BACKGROUND: Allergic diseases can expand at any age as a result of complicated interaction of environmental and genetic factors. Through the years, studies have found that allergic diseases are primarily described by elevated Th2 pathway activation, leading to increased serum IgE levels, allergen reactivity, blood eosinophil counts and secreted interleukins. METHODS: A total of 20 patients with allergy and 20 matched controls participants were recruited for the study. A study was designed with the framework of an ongoing project at the Regional Children's Hospital in Olsztyn on the analysis of the immune profile of children with allergy and asthma. Diagnosis was conducted by medical specialists. Whole blood samples were collected and serum IL's and chemokin levels were made using ELISA kits. RESULTS: Results demonstrated that in comparison to the controls, the individuals with allergy showed significantly higher concentration of IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13 and TNF-α. We also demonstrated significant correlations between the levels of cytokines which implies the presence of an interactive network between them. The results of ROC analysis indicated the 3-factors (IL-1ß, IL-4, IL-8) could be additional, helpful biomarkers in better diagnosis of allergy. CONCLUSIONS: In this study, serum levels of cytokine differed among children with allergy. However, the findings of this support the possibility of using an appropriate selection of serum cytokine for the diagnosis allergy and emphasize the need to standardize quantitative methods for serum analysis.

Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

BACKGROUND: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3 has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. METHODS: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. RESULTS: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3 concentration in serum of ASD children. CONCLUSION: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3 metabolism, while vitamin D3 levels were not significantly different between ASD and non-ASD children.

Changes in gene expression induced by histamine, fexofenadine and osthole: Expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1ß in PBMC allergic and non-allergic patients.

INTRODUCTION: Fexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1ß and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion. OBJECTIVE: The purpose was to investigate expression pattern in asthma PBMC. METHODS: The cultures were treated 72h with FXF and osthole. We measured mRNA expression of histamine HRH-1, COX-2, NF-κB-p50, CCR1, IL-1ß and CCL5/RANTES with Real-Time PCR (RT-PCR). RESULTS: The present study suggest that osthole may be a potential inhibitor of histamine H1 receptor activity. We also demonstrated that cells cultured with histamine increase COX-2 mRNA expression and osthole reduce it. CONCLUSION: Allergy remains one of the most common chronic diseases in Europe and it is rapidly approaching epidemic proportions; with current predictions estimating that the number of allergy-afflicted will equal the healthy population by 2020. It is therefore paramount to find new pharmaceuticals which successfully combat allergic disease.

Cytokine production by PBMC and serum from allergic and non-allergic subjects following in vitro histamine stimulation to test fexofenadine and osthole anti-allergic properties.

FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. This paper compares peripheral blood mononuclear cell (PBMC) incubation with FXF and osthole, by studying FXF, osthole and histamine cytokine secretion in PBMC in vitro cultures. Mabtech kits determined the interleukins IL-1ß, IL-4, IL-10, IL-13 and TNF-α. The influence of the above active substances on cytokine secretion in PBMC's and serum was assessed: cytokines were IL-1ß, IL-4, IL-10, IL-13 and TNF-α; and cytokine levels secreted by untreated PBMCs in pure culture medium formed the absolute control (ctrl). We determined that osthole affects PBMC cytokine secretion to almost precisely the same extent as FXF (IL-1ß, IL-4, IL-10 and TNF). In addition osthole had greater IL-13 blocking ability than FXF. Moreover, we observed significantly decreased IL-4 level in histamine/osthole theatment compared to histamine alone. Meanwhile, FXF not significantly decrease the level of IL-4 increased by histamine. This data indicates osthole's strong role in allergic inflamation. All results confirm our hypothesis that osthole is a natural histamine antagonist and therefore can be beneficially used in antihistamine treatment of conditions such as allergies.

The influence of breast milk and infant formulae hydrolysates on bacterial adhesion and Caco-2 cells functioning.

The aim of the study was to determine the concentration of BCM7 in human milk and infant formulae (IF) before and after eznymatic hydrolysis, and to evaluate the effect of obtained hydrolysates on interleukin-8 (IL-8) secretion and on proliferation of enterocytes in the in vitro model (Caco-2 cells). This study evaluates also the effect of hydrolysates on the adhesion of intestinal microbiota isolated from faeces of both healthy (H) and allergic (A) infants. In the study we investigated breast milk delivered by mothers of healthy ('healthy milk'; HM) and allergic ('allergic milk'; AM) infants. Three infant formulae were investigated: from hydrolysed cow casein (IF1), from hydrolysed cow whey (IF2) and from whole cow milk (IF3). Intestinal bacteria: Bifidobacterium, lactic acid bacteria, Enterobacteriaceae, Clostridium and Enterococcus were isolated from faeces of five healthy and five allergic infants. Mixtures of bacterial isolates and bacteria adhering to Caco-2 cells were characterised qualitatively with PCR-DGGE, and quantitavely with FISH. Concentration of BCM7 in breast milk and infant formulae was 1.6 to 8.9 times higher after enzymatic hydrolysis in comparison to undigested samples. The presence of this peptide resulted in alteration of intestinal epithelial proliferation and increase in secretion of IL-8. The quantitative profile of adherred bacteria applied as a mix of all isolates from healthy infants (H-MIX) was unchanged in the presence of HM hydrolysate and was modulated (increased number of beneficial Bifidobacterium and reduced commensal Enterobacteriaceae) in the presence of all IF hydrolysates. The presence of IF hydrolysates affected the profile of adhering isolates obtained from allergic infants (A-MIX) and reduced the adhesion of Enterobacteriaceae; the IF2 and IF3 hydrolysates decreased also the total number of adhering bacteria (TBN). However, a stimulating effect of AM hydrolysate on A-MIX adhesion (increased TBN) was observed.

Impact of fexofenadine, osthole and histamine on peripheral blood mononuclear cell proliferation and cytokine secretion.

This paper compares results of peripheral blood mononuclear cell (PBMC) incubation with fexofenadine (FXF) and osthole. FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. To our best knowledge, this is the first comparative study on FXF, osthole and histamine cytokine secretion and cytotoxicity in PBMC in vitro cultures using cell proliferation ELISA BrdU. The cultures were treated 12, 42, 48 and 72h with FXF and osthole at 150, 300 and 450ng/ml concentrations and histamine at 50, 100 and 200ng/ml. Our study results confirm that FXF, osthole and histamine exert no cytotoxic effect on PBMCs and that IL-6, IL-10 and TNF-α cytokine secretion following osthole cell stimulation was similar to that by FXF stimulation.This confirms our hypothesis that osthole is a natural histamine antagonist, and can therefore be beneficially applied in antihistamine treatment.

µ-Opioid receptor gene (OPRM1) polymorphism in patients with breast cancer.

Structure-dependent µ-opioid receptor (MOR) activity is an important element in cancer opioid analgesic effectiveness. It is widely accepted that guanine (G) substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor glycosylation pattern. This is associated with decreased binding ability in both exogenous and endogenous opioids, resulting in increased human pain resistance. The endogenous opioid system's function in body homeostasis maintenance is considered mainly regulatory, so its participation in breast tumor formation and progression is identified herein. We examine the association of the most frequent MOR (A118G) gene polymorphism on breast cancer risk in a Northeastern Polish population by PCR-RFLP comparison of A and G allele frequency at OPRM1 gene A118G polymorphic site in breast cancer-diagnosed patients with healthy control group frequencies. Our results highlight a strong association between G allele presence at µ-opioid receptor A118G and increased breast cancer incidence (OR = 3.3, 95 % CI 2.2-5.0, p < 0.0001) and female gender (OR = 2.0, 95 % CI 1.4-2.9, p = 0.0004). Consequently, OPRM1 G allele presence at that site is a highly significant risk factor in breast cancer development.

Influence of candidate polymorphisms on the dipeptidyl peptidase IV and µ-opioid receptor genes expression in aspect of the ß-casomorphin-7 modulation functions in autism.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with population prevalence of approximately 60-70 per 10,000. Data shows that both opioid system function enhancement and opiate administration can result in autistic-like symptoms. Cow milk opioid peptides, including ß-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile), affect the µ-opioid receptor (MOR) and are subjected to degradation resulting from the proline dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) enzyme activity. The presence of MOR and DPPIV activity are crucial factors determining biological activity of BCM7 in the human body. Our study examined the effect of ß-casomorphin-7 on the MOR and DPPIV genes expression according to specific point mutations in these genes. In addition, we investigated frequency of A118G SNP in the MOR gene and rs7608798 of the DPPIV (A/G) gene in healthy and autistic children. Our research indicated correlation in DPPIV gene expression under the influence of BCM7 and hydrolyzed milk between healthy and ASD-affected children with genotype GG (P<0.0001). We also observed increased MOR gene expression in healthy children with genotype AG at polymorphic site A118G under influence of BCM7 and hydrolyzed milk. The G allele frequency was 0.09 in MOR gene and 0.68 in the DPPIV gene. But our results suggest no association between presence of the alleles G and A at position rs7608798 in DPPIV gene nor alleles A and G at position A118G of the MOR and increased incidence of ASD. Our studies emphasize the compulsion for genetic analysis in correlation with genetic factors affecting development and enhancement of autism symptoms.