Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level.

(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730C (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730C gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14-7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05-3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09-2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08-0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07-0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74-5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. MATERIALS AND METHODS: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. RESULTS: There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). CONCLUSIONS: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

Determining Factors of Arterial Stiffness in Subjects with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MS) is a clustering entity characterized by obesity, hypertension, hyperglycemia, dyslipidemia, and insulin resistance. Early detection of atherosclerosis is important in patients with MS because cardiovascular diseases are the main cause of mortality in these patients. METHODS: We aimed to investigate the factors influencing arterial stiffness, pulse wave velocity, and the augmentation index, respectively, in 150 subjects with MS (94 women and 56 men; mean age 60.56 ± 9.8 years). Arterial stiffness was measured using the TensioMed™ Arteriograph. We tested the relationship between arterial parameters and insulin resistance measured by the determination of insulinemia (the ELISA method) and the homeostasis model assessment index (HOMA). RESULTS: In multivariate analysis we identified the independent factors that influence arterial stiffness: systolic blood pressure (coefficient of determination 3.586; P < 0.0001), serum triglycerides (coefficient of determination 3.579; P < 0.0001), and age (coefficient of determination 3.510; P = 0.001) are independent predictive factors for pulse wave velocity. The independent predictive factors of the augmentation index were the body mass index (coefficient of determination 0.55; P = 0.009), the presence of diabetes mellitus (coefficient of determination 4.7; P = 0.03), mean arterial pressure (coefficient of determination 0.44; P < 0.0001), gender (coefficient of determination 9.2; P < 0.0001), age (coefficient of determination 0.3; P < 0.0001), and heart rate (coefficient of determination 0.66; P < 0.0001). Insulin resistance (HOMA index) was a predictor of the brachial augmentation index (ß coefficient 3.4; P < 0.001) and was not a predictor of pulse wave velocity (ß = -0.3; P = 0.6) in our study. CONCLUSIONS: Given the known predictive value of pulse wave velocity for cardiovascular events, identifying the factors responsible for the increase in arterial stiffness is extremely important.

Non-invasive assessment of liver fibrosis in chronic viral hepatitis.

BACKGROUND: Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT ratio, Fibrosis 4 score (FIB4) and FibroScan were studied as non-invasive markers of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of F. The aim of our research was to study whether HA, APRI, ASAT/ALAT ratio, FIB4 and FibroScan are useful non-invasive markers in predicting severe F in Romanian patients. PATIENTS AND METHODS: This was a prospective multicenter transversal and observational study, which included 76 patients with CHB/CHC. The independent effect of studied markers was tested using multiple binary logistic regression. RESULTS: In patients with CHB and CHC, the APRI cut-off value for F4 was 0·70 ng/mL (Se = 77%, Sp = 78%), the FIB4 cut-off value was 2·01 (Se = 77%, Sp = 69%), and the FibroScan cut-off value was 13·15 (Se = 92%, Sp = 88%). For patients with CHB/CHC, there was a significant linear positive correlation between F and HA (r = 0·42, P = 0·001), FibroScan (r = 0·67, P < 0·001), APRI (r = 0·46, P < 0·001) and FIB4 (r = 0·51, P < 0·001). Considering age, sex and body mass index as possible confounding factors or covariates in multivariable logistic modelling, FibroScan was the unique test that able to significantly highlight the presence of F4 score in CHB/CHC patients (P = 0·009) while FIB4 test seems to have a tendency to statistical significance. CONCLUSION: FibroScan, APRI and FIB4 are useful non-invasive tests for the evaluation of F4 in patients with CHB and CHC.

Paraoxonase 1 genotype-phenotype correlation in patients with metabolic syndrome.

The aim of the study was to investigate the influence of three single nucleotide polymorphisms (SNPs) (-108C>T, -162A>G and -909G>C) from the promoter region of paraoxonase 1 (PON1) gene on the enzyme activity, in patients with metabolic syndrome (MS). The study group consisted of 61 individuals with MS and the control group of 73 individuals without MS, matched for age and gender. For each individual, clinical and genetic parameters with possible influence on PON1 activities (paraoxonase, arylesterase and lactonase) were measured. PON1 genotyping was performed with PCR-RFLP, using specific primers and restriction enzymes. We found no differences for distribution of PON1 -108C>T, -162A>G and -909G>C polymorphisms, between the two groups (p-NS). The -108C>T and -909G>C polymorphisms were associated with paraoxonase (p=0.03, p=0.006, respectively), arylesterase (p<0.001, p<0.001, respectively) and lactonase (p<0.001, p<0.001, respectively) activities. The -162A>G polymorphism was not associated with paraoxonase (p-NS) or lactonase (p-NS) activities, but influenced the arylesterase activity (p=0.03). PON1 activities were influenced by all three polymorphisms, regardless of the presence of MS.

Cardiac amyloidosis with gastrointestinal involvement: a case report.

Familial amyloidosis is a rare type of amyloidosis, difficult to diagnose. We present the case of a woman with chronic heart failure. Low ejection fraction and concentric left ventricle hypertrophy with granular sparkling were seen by echocardiography and cardiac magnetic resonance imaging. Based on myocardial biopsy and genetic tests, the diagnosis of transthyretin familial amyloidosis, secondary to the Glu54Gln gene mutation, was made. The presentation contains the diagnostic algorithm used in the case of our patient, including clinical, biochemical, imaging, histological and genetic examinations, for the purpose of a complete diagnosis.

Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis.

INTRODUCTION: Hyperhomocysteinemia is considered an independent risk factor for cardiovascular disease. Oxidative stress is one of the major pathogenic mechanisms in non-alcoholic fatty liver disease and atherosclerosis. AIM: Our study aimed to evaluate serum homocysteine levels and oxidative stress in patients with biopsy-proven non-alcoholic steatohepatitis and possible association with cardiovascular risk measured by carotid artery intima-media thickness (c-IMT). PATIENTS AND METHODS: 50 patients with non-alcoholic steatohepatitis and 30 healthy controls, age and gender matched, were recruited. Lipid profile, liver biochemical markers, serum homocysteine, vitamins B6 and B12, folic acid, glutathione (reduced and total), erythrocyte superoxide dismutase, whole blood glutathione peroxidase, malondialdehyde and carotid intima-media thickness were assayed. RESULTS: Patients had an altered lipid profile and liver biochemical markers; carotid intima-media thickness and serum homocysteine levels were significantly higher compared to controls, but there were no differences in folate, B12 and B6 vitamins levels. Patients had significantly lower levels of glutathione peroxidase activity, total and reduced glutathione and higher levels of malondialdehyde, but unchanged superoxide dismutase activity compared to control group. Also, serum homocysteine level showed significant positive correlation with waist circumference, body mass index, free cholesterol, triglycerides, LDL-cholesterol, amino transferases and negative correlation with reduced and total glutathione, superoxide dismutase and γ-GT. CONCLUSION: Non-alcoholic steatohepatitis is an independent cardiovascular risk factor, associated with elevated homocysteine levels, oxidative stress and c-IMT. c-IMT could be used as an indicator of early atherosclerotic changes initiated by dyslipidemia and oxidative stress, while higher level of homocysteine might be an effect of liver damage.

Pancreatic hamartoma and SAPHO syndrome: a case report.

We report the first case of an association of pancreatic hamartoma with SAPHO syndrome mimicking disseminated bone metastases. A 46 year old male with intermittent back pain for 10 years, relieved by NSAIDs and desquamation erythemathous palmo-plantar eruption one year before, presented with symptoms of duodenal stenosis, a cystic tumor at the head of the pancreas and osteoformative (hyperostosis) and osteodestructive (osteitis) lesions of the clavicle, mandible, lumbar spine. The bone lesions resembled bone metastases, but an inflammatory infiltrate and fibrosis were found on the excisional biopsy of left clavicle, compatible with the SAPHO syndrome. The pancreatic tumor grew rapidly and showed a histological aspect of malignancy at laparoscopy. A cephalic duodenopancreatectomy was performed, but the histological findings established the diagnosis of pancreatic hamartoma. Several months later, the bone Tc99m scintigraphy was normal.