A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (AR), and systemic lupus erythematosus (SLE). Vitamin D is a potent immunonutrient that through its main metabolite calcitriol, regulates the immunomodulation of macrophages, dendritic cells, T and B lymphocytes, which express the vitamin D receptor (VDR), and they produce and respond to calcitriol. Genetic association studies have shown that up to 65% of vitamin D serum variance may be explained due to genetic background. The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the vitamin D binding protein (VDBP; rs2282679 GC), 25-hydroxylase (rs10751657 CYP2R1), 1α-hydroxylase (rs10877012, CYP27B1) and the vitamin D receptor (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) VDR). Therefore, the aim of this comprehensive literature review was to discuss the current findings of functional SNPs in GC, CYP2R1, CYP27B1, and VDR associated to genetic risk, and the most common clinical features of MS, RA, and SLE.

https://www.mdpi.com/1422-0067/21/24/9626/pdf

Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies

Background
Improving prediction of treatment outcomes in chronic hepatitis C (CHC) genotype 4 (G4) is necessary to increase sustained viral response (SVR) rates. Vitamin D related and interferon stimulated genes are good candidates as they are recently crosstalk altering interferon response. Thus single nucleotide polymorphisms (SNPs) within some of these genes and multiple stepwise regression analysis including other independent predictors (IL28B(rs12979860), serum 25OH-vitamin D, serum alfa-fetoprotein (AFP)) were performed on a cohort of 200 Egyptian CHC patients treated with Pegylated interferon-alpha (Peg-IFN) plus ribavirin.

/pdf/integrative-role-of-vitamin-d-related-and-interleukin-28b-39zgoy7jil.pdf

Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C

AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.

RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation.

CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

Role of genetic polymorphisms in hepatitis C virus chronic infection.

Aims: This study was designed to determine if vitamin D receptor (VDR), carrier globulin/binding protein (GC), and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) gene polymorphisms ...

Role of VDR, GC, and CYP2R1 Polymorphisms in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients

Background: Colonoscopies are carried out for a range of reasons including for the detection of colon cancer and investigation of abdominal and bowel related symptoms. Inadequate preparation can increase the burden of repeat procedures.Methods: A systematic review aimed to identify the rate of repeat colonoscopies due to inadequate bowel preparation in France, Germany, Italy, Spain and the United Kingdom. The information obtained populated a decision analytic model to estimate the cost implications of inadequate bowel cleansing in the same five countries. The model explored scenarios by comparing one and two-litre polyethylene glycol-based bowel preparation.Results: The systematic review identified 14 eligible studies reporting on the proportion of patients with inadequate bowel cleansing indicated for a repeat procedure. Data were available for Italy (27.5%-35.9%), Spain (63%) and the UK (24.5%) only. The decision analytic model demonstrates that improving the proportion of adequate bowel cleansing at first colonoscopy is likely to generate cost savings.Conclusions: Based on the available evidence, increasing the proportion of people who have adequate bowel cleansing at index colonoscopy will likely have financial benefits in Italy, Spain and the UK. A paucity of data, for France and Germany, limits the robustness of conclusions in these countries.

A systematic review and cost analysis of repeat colonoscopies due to inadequate bowel cleansing in five European countries.

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality in Western countries. As for most other cancers, it is likely that CRC represents an interaction between genetic and environmental factors. Since genetic factors are a cause in only a minority of cases, environmental factors, particularly diet, are probably prevalent. Many studies have shown that an increase in meat consumption produces a clear increase in CRC. However, the difference is mostly in the extreme classes of meat intake (i.e. between people who eat a large amount of meat every day and those who hardly ever eat red meat). Moreover, the difference in risk is only 12-17% for an increase of 100 g/day in meat intake, probably not enough in itself to warrant large-scale campaigns to reduce meat intake. Similar conclusions can be drawn from the relationship between an increase in fruit, fiber, or milk intake and a decrease in CRC. However, all the suggested changes move towards a healthier diet, which also has positive effects on other highly prevalent disorders (cardiovascular, degenerative, and neoplastic). Sound dietary advice should therefore be offered even in the absence of formal evidence-based proof.

Diet, Polyps, and Cancer Where is the Truth?

P.18.3 early wake up, one day low fiber diet: split bowel even for patients undergoing colonoscopy early in the morning. a real life experience

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality in Western countries. As for most other cancers, it is likely that CRC repre- sents an interaction between genetic and environmental factors. Since genetic factors are a cause in only a minority of cases, environmental factors, particularly diet, are probably prevalent. Many studies have shown that an increase in meat consumption produces a clear increase in CRC. However, the difference is mostly in the extreme classes of meat intake (i.e. between people who eat a large amount of meat every day and those who hardly ever eat red meat). Moreover, the difference in risk is only 12-17% for an increase of 100 g/day in meat intake, probably not enough in itself to warrant large-scale campaigns to reduce meat intake. Similar conclusions can be drawn from the relationship between an increase in fruit, fiber, or milk intake and a decrease in CRC. However, all the suggested changes move towards a healthier diet, which also has positive effects on other highly prevalent disorders (cardiovascular, degenerative, and neoplastic). Sound dietary advice should therefore be offered even in the absence of formal evidence-based proof.

http://link.springer.com/content/pdf/10.1007/978-88-470-1124-3_6.pdf

Diet, Polyps, and Cancer

10 Pancreogastro Anastomosis Is Associated With a More Severe Derangement of Pancreatic Function and a More Marked Reduction of Pancreatic Volume Than Pancreojejunal Anastomosis. Results of a Long-Term Follow-Up Study After Duodenopancreatectomy

Vitamin D serum levels seem to influence antiviral response in chronic hepatitis C. Vitamin D pathway is controlled by genes presenting functional single nucleotide polymorphisms (SNPs). Data regarding the association between these polymorphisms and the rate of sustained viral response (SVR) following antiviral treatment in chronic hepatitis C virus (HCV) infection are largely incomplete. Aim of this study was to evaluate if the carriage of different SNPs of these genes could influence the rate of SVR in patients treated with interferon plus ribavirin. Two hundred and six HCV positive patients treated with PEG-interferon plus ribavirin were retrospectively evaluated. Polymorphic loci rs7041 G>T and rs4588 C>A of the vitamin D transporter GC-globulin, rs10741657 G>A of the vitamin D 25 hydroxylase CYP2R1 and rs10877012 G>T of vitamin D 1-hydroxylase CYP27B1 were genotyped. A genetic model named VDPFA (vitamin D Pathway Functional Alleles) was constructed considering for each patient the sum (from 0 to 8), derived from every functional allele carried, associated with the achievement of SVR. Three groups were identified: those carrying ≤4 VDPFA (N=108), those carrying 5-6 VDPFA (N=78) and those carrying ≥7 VDPFA (N=20). Significant associations were found between the rates of SVR and the VDPFA value both in all (61/108, 53/78, 17/20, p=0.009) and in 1/4-5 HCV genotypes (17/56, 23/43, 6/8, p=0.003). Moreover in patients who don’t achieve rapid viral response (RVR) SVR and VDPFA were found to be in stronger associations in all (12/55, 17/39, 7/9, p<0.001) and in 1/4-5 HCV genotypes (4/41, 12/31, 5/6, p=0.001). VDPFA value ≥7 could aid to select, among RVR negative difficult to treat 1/4-5 HCV genotypes, those achieving SVR. These observations could permit to extend the indication to adopt dual antiviral therapy beyond RVR positivity rule without reducing the chances of SVR.

Genetic Polymorphisms of Vitamin D Pathway Predict Antiviral Treatment Outcome in Slow Responder Naïve Patients with Chronic Hepatitis C

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