•In vitro investigation of the impact of the polymorphisms of the 3′ UTR of the SLC11A1 gene to its expression.•The infection induced by the M. avium ssp. paratuberculosis to macrophages causes ...upregulation of the SLC11A1 gene.•The data presented here demonstrate that the homozygous B7 genotype leads to up-regulation of the SLC11A1 and IL-1α genes.•B7/7 genotype indicates increased responsiveness of macrophages to MAP exposure compared to the B8/8 and B7/B8 genotypes.
Johne’s disease or paratuberculosis is a chronic, progressive intestinal disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). One of the genes that have been targeted with regard to resistance or sensitivity to paratuberculosis is the SLC11A1 (solute carrier family 11 member A1). Here we extend our previous work to the sequence and structure analysis of the caprine SLC11A1 gene and we assess the functional impact of the most frequent polymorphisms of the 3′ UTR region of the SLC11A1 gene to its expression in goat macrophages exposed in vitro to MAP. The role of these polymorphisms in primary immune response is also investigated with connection to gene expression of two interleukins (IL), one of which pro (IL-1a), and the other anti-inflammatory (IL-10). In order to assess gene response, quantitative detection of the SLC11A1, IL-10 and IL1a mRNA was performed by real time PCR before, and at 1, 3 and 24h after exposure of primary cultures of peripheral blood monocyte-derived macrophages to MAP, collected from 54 goats of the Greek native goat breed. Sequence analysis of the 3′ UTR end of the caprine SLC11A1 gene determined its full length to be 522 bases. Structure analysis confirmed the presence of two microsatellites consisted of a variable number of guanine-thymine repeats (regions A and B). The homozygous B7 genotype B(GTn)7/7 was associated at a statistically significant level with increased expression of the SLC11A1 and IL-1α genes indicating increased in vitro responsiveness and therefore resistance of mononuclear derived macrophages to MAP infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Polymorphisms in the serotonin transporter (SERT) and G protein β3 subunit (GNB3) genes might contribute to the pathophysiology of irritable bowel syndrome (IBS). Association studies of ...SERT and GNB3 polymorphisms and IBS have shown diverse results among different populations, which might be due to subject composition differences.
Aims
The aim of the study was to assess the potential association between SERT and GNB3 polymorphisms and IBS in Greeks.
Methods
A total of 124 patients with IBS diagnosed according to the Rome III criteria and 238 healthy individuals were included in the study. SERT and GNB3 gene polymorphisms were genotyped using polymerase chain reaction-based methods.
Results
It was shown that the frequencies of the SS genotype and S allele of the serotonin transporter polymorphism were significantly associated with IBS (
P
= 0.0314 and
P
= 0.019, respectively). TT genotype and T allele frequencies of G protein β3 subunit showed also significant difference between the IBS patients and healthy controls IBS (
P
= 0.0163 and
P
= 0.0001, respectively). None of the clinical symptoms analyzed was significantly associated with the polymorphisms tested.
Conclusions
The results suggest that SERT and GNB3 gene polymorphisms might be associated with irritable bowel syndrome predisposition in Greeks.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The aim of the present study was to assess the presence of single nucleotide polymorphisms (SNPs) in the Growth Differentiating Factor 9 (GDF9) and Bone Morphogenetic Protein 15 (BMP15) genes, in two ...Greek sheep breeds i.e. Chios and Karagouniki, with high and moderate litter size (LS) i.e. number of lambs born, respectively. An examination of association(s) between the polymorphisms and LS, within breeds, was also conducted. Blood samples from 92 Chios and 96 Karagouniki ewes were collected, while repeated records on LS, were also available (n=239 and 259, respectively). Detection of SNPs was performed on the DNA products by PCR-RLFP analysis. Data analysis included examination of allelic and genotypic differentiation between the breeds, testing for Hardy–Weinberg Equilibrium (HWE) and association analysis between polymorphisms and LS. Genetic analysis showed that the G1 and G8 mutations of the GDF9 gene were significantly over-presented only in the highly prolific breed (Chios). The B4 mutation of the BMP15 gene was significantly over-presented only in the low prolific breed (Karagouniki). Both breeds were in Hardy–Weinberg disequilibrium (HWD), possibly due to selection pressure, population sub-structure and genetic drift. Certain polymorphisms of the G1, G4 and G8 sites of the GDF9 gene in the Chios breed were found to show heterozygote advantage with no evidence of infertility for the homozygous females. A similar trend was observed in the BMP15 gene although at no statistically significant level. In the Karagouniki breed, no significant associations between the studied polymorphisms and LS were detected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of the study was to examine the frequency and relationship of peroxisome proliferator‐activated receptor (PPAR)‐γ and PPAR‐δ gene polymorphisms to polycystic ovary syndrome (PCOS) ...characteristics. We conducted a case‐control study protocol, which included 183 PCOS women and 148 healthy volunteers. Genetic, clinical, hormonal, and metabolic characteristics of PCOS patients and controls were estimated and compared. Genotype and allele frequencies did not differ significantly. The Pro12Ala polymorphism in exon 2 of the PPAR‐γ gene was found in low frequency. Regarding the polymorphism in exon 6, the T‐allele carrier PCOS women had significantly lower total testosterone levels. Regarding the +294T/C polymorphism in the exon 4 of the PPAR‐δ gene, the C‐allele carrier PCOS women had significantly higher fasting glucose levels. In conclusion, the PPAR‐γ gene polymorphisms do not appear to affect the risk for PCOS, except for the reduced testosterone levels. The +294T/C polymorphism in the exon 4 of the PPAR‐δ gene seems to cause an increase in fasting glucose levels.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Bevacizumab, an angiogenesis inhibitor is used in regimens for metastatic colorectal cancer (CRC). A minority of cancer cells with characteristics of cancer stem cells (CSC) may be responsible for ...progression and development of chemotherapy resistance in this disease. CD133 is a well-known CSC marker and is associated with angiogenesis, poor prognosis and resistance to chemotherapy.
The purpose of our study was to evaluate the association between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the response, toxicity, and overall survival of patients with CRC on bevacizumab-based treatment.
Forty-three patients receiving bevacizumab, irinotecan and capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were included. Efficacy and toxicity were evaluated. KRAS mutation analysis and rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR-RFLP.
No association between KRAS mutated alleles and response was found. The rs3130 CC genotype was associated with reduced toxicity of treatments (p= 0.0017), and with lower overall survival on bevacizumab (p= 0.002).
The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
The inflammatory bowel disease (iBD) etiology remain elusive and both genetic and environmental factors have been implicated in the establishment of systemic inflammatory ...reactions that typify IBD. A basic, modifiable environmental factor is the gut microbiota and dysbiosis seems to be a key factor in IBD pathogenesis. Nowadays, it is well known that anti-TNF therapy significantly improves the rates of remission in patients with inflammatory bowel disease (IBD), however, there is a subgroup of patients who do not respond to treatment. The aim of the present study is to profile changes in the mucosal gut microbiome before and after anti-TNF therapy and investigate its possibility to predict patient response at baseline.
Methods
Mucosal biopsy samples from IBD patients 14 Crohn’s disease patients (CD), 6 ulcerative colitis (UC) patients and healthy controls (HC) were examined for differences in microbiota composition (16S rRNA gene sequencing) at baseline and upon completion of anti-TNF treatment, accordingly, via an in silico pipeline.
Results
Although no statistically significant differences at phylum level were noted, a relative reduction in Bacteroidetes and an increase in Actinobacteria, Fusobacteria and Chloroflexi were detected in IBD versus HC biopsies, however the microbiomes of UC, CD and HC display qualitative differences at the OTU level. At genus level, statistically significant differential abundance between the HC and IBD groups was observed. The genera Parabacteroides, Barnesiella, Butyricimonas, Ruminococcus_1, Ruminococcaceae_UCG013, Phascolarctobacterium, Ruminoclostridium_6, Paraprevotella as well as members of the Eubacterium_ruminantium group appear reduced in IBD, whereas Dialister abundance is increased. The genus Collinsella exhibits an induction during UC versus both HC and CD. Regarding anti-TNF treatment on the microbiome, Alpha-diversity is reduced after anti-TNF treatment. Beta-diversity indicates differences before and after treatment as well as between responders and non-responders. By using the biomarker discovery tool LEfSe, we identified microbial genera associated mainly with anti-TNF responders.
Conclusion
In the present study, we showed that the response to anti-TNF therapy is related to specific microbiota profiles in the gut mucosa. Correlation analysis between these parameters of response at baseline showed that the assessment of microbial taxa can further distinguish responders from non-responders.
Personalized Medicine is more than just a metabolic activity of a person. Pharmacogenomics, pharmacogenetics, pharmacoproteomics, and metabolomics play an important role in the development of ...personalized medicines. Personalized medicine uses information about a person's genes, proteins, enzyme activities, and cellular environment to diagnose and treat disease, cancer included. A major problem of personalized medicine is the fact that there is no portable bedside and low-cost bioanalytical technology that can be used in close proximity to the patient. This technology could play a significant role in defining the dosage setting for subsets of the population. The success of the personalized therapy is possible through the application of technology, which can provide a bridge between metabolism status and an individual's response to a particular drug and therapeutic modality.
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