Djordje Culafic

siMS Score: Simple Method for Quantifying Metabolic Syndrome

Objective To evaluate siMS score and siMS risk score, novel continuous metabolic syndrome scores as methods for quantification of metabolic status and risk. Materials and Methods Developed siMS score was calculated using formula: siMS score = 2*Waist/Height + Gly/5.6 + Tg/1.7 + TAsystolic/130—HDL/1.02 or 1.28 (for male or female subjects, respectively). siMS risk score was calculated using formula: siMS risk score = siMS score * age/45 or 50 (for male or female subjects, respectively) * family history of cardio/cerebro-vascular events (event = 1.2, no event = 1). A sample of 528 obese and non-obese participants was used to validate siMS score and siMS risk score. Scores calculated as sum of z-scores (each component of metabolic syndrome regressed with age and gender) and sum of scores derived from principal component analysis (PCA) were used for evaluation of siMS score. Variants were made by replacing glucose with HOMA in calculations. Framingham score was used for evaluation of siMS risk score. Results Correlation between siMS score with sum of z-scores and weighted sum of factors of PCA was high (r = 0.866 and r = 0.822, respectively). Correlation between siMS risk score and log transformed Framingham score was medium to high for age groups 18+,30+ and 35+ (0.835, 0.707 and 0.667, respectively). Conclusions siMS score and siMS risk score showed high correlation with more complex scores. Demonstrated accuracy together with superior simplicity and the ability to evaluate and follow-up individual patients makes siMS and siMS risk scores very convenient for use in clinical practice and research as well.

The Polymorphism rs3024505 (C/T) Downstream of the IL10 Gene Is Associated with Crohn’s Disease in Serbian Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), manifesting as Crohns disease (CD) and ulcerative colitis (UC), is characterized by recurring episodes of inflammation in gastrointestinal tract, in which aberrant production of regulatory cytokine interleukin-10 (IL-10) presumably plays important role. Single nucleotide polymorphisms (SNPs) that affect IL-10 production, such as rs1800896 (G/A) at position -1082 and rs1800871 (C/T) at position -819 in the promoter region of the IL10 gene, have been associated with CD and/or UC, but the results were inconsistent. Another SNP that may alter IL-10 production, rs3024505 (C/T) located immediately downstream of the IL10 gene has been recently identified. T allele of rs3024505 was associated with both UC and CD in Western populations, but the studies from East European countries are lacking. Therefore, our aim was to assess the association of rs3024505, rs1800896 and rs1800871 with Serbian IBD patients. To this end, 107 CD and 99 UC patients and 255 healthy controls were genotyped. As a result, T allele of rs3024505 was associated with CD at allelic, genotypic (GT genotype) and haplotypic (GCCT haplotype) level, suggesting potential role of this variant in susceptibility to CD. In contrast, CD patients carrying C allele of rs3024505 had significantly increased risk of anemia and stricturing/penetrating behavior. No association was observed between rs3024505 and UC or SNPs in IL10 promoter region and any form of IBD. In conclusion, rs3024505 SNP flanking the IL10 gene is associated with susceptibility and severity of disease in Serbian CD patients, further validating its role as a potential biomarker in IBD.

Liver function test changes in centrally obese youth with metabolic syndrome in a Serbian population.

OBJECTIVE The aim of this study was to investigate the association between metabolic syndrome and liver enzymes in overweight and obese adolescents and young adults. METHODS A total of 126 overweight and obese adolescents and young adults (age, 15-26 years), 55 (43.6%) with metabolic syndrome and 71 (56.4%) without metabolic syndrome, were studied. RESULTS Patients with metabolic syndrome had significantly higher alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) levels compared to patients without metabolic syndrome [36.5±22.2 vs. 29.4±17.8 IU/L (P=0.043), 33.8±17.8 vs. 26.9±18.4 IU/L (P=0.002), and 84.3±32.2 vs. 75.7±29.5 IU/L (P=0.063)]. Aspartate aminotransferase (AST) levels were similar in both groups (24.1±9.8 vs. 23.3±9.0 IU/L, P=0.674). Elevated AST, ALT, GGT, and ALP levels were observed in 6, 15, 18, and 5 patients (11%, 27%, 14%, and 9%) with metabolic syndrome compared to 6, 17, 6, and 4 (8%, 24%, 8% and 5%) patients without metabolic syndrome (P=0.872, P=0.826, P<0.001, and P=0.035). In multivariate regression models adjusted for age and gender, metabolic syndrome was not a significant predictor of ALT (P=0.967), GGT (P=0.526), and ALP levels (P=0.221), but insulin resistance was a significant predictor for ALT and GGT levels (P=0.001, P=0.028). CONCLUSION Changes in liver function tests were observed in obese patients with metabolic syndrome, compared to patients without metabolic syndrome, especially in ALT and GGT levels. Insulin resistance is an independent pathogenic mechanism in liver function test changes regardless of metabolic syndrome in nondiabetic centrally obese youth.

MDR1 gene polymorphisms are associated with ulcerative colitis in a cohort of Serbian patients with inflammatory bowel disease

Background Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients. Methods A total of 206 IBD patients, 107 Crohns disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons. Results Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed. Conclusion MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC.

The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis

Background: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. Methods: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. Results: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 ± 0.06) and there was the statistically significant difference compared to controls (0.66 ± 0.03) (p < 0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child–Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. Conclusion: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.