Lada Zibar

Association Studies of Gene Polymorphisms in Toll-Like Receptors 2 and 4 in Croatian Patients with Acute Myocardial Infarction

The aim of the study was to assess the frequency of SNP896A/G in the Toll‐like receptor (TLR) 4 gene and SNP1350T/C in the TLR2 gene in patients with acute myocardial infarction (AMI) and to analyse the association of these SNPs with risk factors for atherosclerosis and clinical aspects of AMI in a sample of the Croatian population. We included 240 participants in the study: 120 AMI patients and 120 sex‐ and age‐matched healthy blood donor controls. The SNP1350T/C variant in the TLR2 gene showed a lower frequency in the AMI patient group than in the control group (P = 0.033). The frequency of SNP896A/G variants in the TLR4 gene between the patients and the controls did not differ (P = 0.286). Significantly, fewer people had SNP1350T/C in the TLR2 gene (P = 0.003) among the participants with arterial hypertension than those without it. The frequency of SNP896A/G in TLR4 was the same in hypertensive patients compared with normotensive subjects (P = 0.088). SNP1350T/C in TLR2 was less frequent in the AMI patients and in those with hypertension. Thus, SNP1350T/C in TLR2 might play a protective role against AMI and arterial hypertension. The frequency of SNP896A/G in the TLR4 gene was not associated with AMI and arterial hypertension. Other risk factors for atherosclerosis and clinical aspects of myocardial infarction were not associated with the genotype distribution of the examined genes.

Human leptospirosis in eastern Croatia, 1969–2003: Epidemiological, clinical, and serological features

This survey presents epidemiological, serological and clinical features of 270 patients (85% males, 18% children) treated for leptospirosis from 1969 to 2003 at the Clinic for Infective Diseases, University Hospital Osijek, Osijek, eastern Croatia. 75% of the admissions were between July and October. The route of transmission was mostly by indirect contact with domestic animals, less frequently by direct contact with urine or tissue of infected animals. Clinical presentation included signs and symptoms with expected and common frequency, with the exception of jaundice (62%) and aseptic meningitis (60%), which occurred with higher incidence than previously reported. Acute renal failure ensued in 53% of patients, 7% of whom required haemodialysis. No deaths were observed. Therapy consisted of antimicrobials (penicillin and doxycycline) and symptomatic measures. Diagnosis was confirmed by microscopic agglutination test (MAT). There were in total 18 serological types of Leptospira detected, and types L. sejroe, L.pomona, L. australis and L. icterohaemorrhagiae prevailed. During the last 10 y some new types were observed. Leptospirosis was not rare in the region of eastern Croatia, and its course could be life-threatening if not recognized and adequately treated.

The relationship between interferon-γ gene polymorphism and acute kidney allograft rejection.

Cytokine gene polymorphisms have been associated with modified gene expression and cytokine production. Gamma interferon (IFN‐γ) plays an important role in the pathogenesis of kidney transplant rejection. This study evaluated the association between IFN‐γ gene polymorphisms and the history of acute allograft rejection in 53 adult first‐transplant recipients receiving cadaveric kidney grafts. They were followed up in a single centre until 2006, for a median time of 4 years after transplantation (1–22 years). IFN‐γ gene polymorphisms +874 T/A (rs2430561) were determined by polymerase chain reaction (PCR). T/T high IFN‐γ genotype was found in 12, intermediate T/A in 29 and low A/A in 12 patients. Twenty‐six acute kidney rejection episodes were evidenced in 20 patients, of which none occurred in the 12 patients with low IFN‐γ genotype A/A. Age, gender, number of HLA (human leukocyte antigen) mismatches, ABO blood groups, HLA, time after transplantation, creatinine clearance and immunosuppressive regimens were excluded as confounding factors associated with IFN‐γ genotype distribution between rejectors and non‐rejectors. IFN‐γ gene polymorphisms could be an important risk factor for acute kidney transplant rejection, whereas the low A/A IFN‐γ genotype could be protective against rejection.

Genetic variation in leptin and leptin receptor genes is a risk factor for idiopathic recurrent spontaneous abortion

Aim To determine whether maternal leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with idiopathic recurrent spontaneous abortion (IRSA). Methods This case-control association study conducted from 2010 to 2012 at the Department of Gynecology and Obstetrics, University Hospital Center Osijek and Clinical Institute of Medical Genetics Ljubljana included 178 women with a history of three or more IRSAs before the 22nd week of gestation and 145 women with at least two live births and no history of pathologic pregnancies during reproductive period. Polymorphisms of maternal LEP (rs7799039, rs2122627, rs11761556, rs10244329) and LEPR (rs1137101, rs7516341, rs1186403, rs12062820) were assessed by allele specific real-time polymerase chain reaction. Genotype distribution, allele frequencies, and frequency of haplotypes at LEP and LEPR genetic loci were determined. Results We observed more frequent genotype for rs7516341 (nominal P = 0.034, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.38-0.97) and rs1137101 (nominal P = 0.048, OR 1.66, 95% CI 1.00-2.80) in the LEPR gene in patients than in controls, but these results did not remain significant after correction for multiple testing according to Bonferroni (adjusted P value threshold was set at 0.05). We did not observe differential distribution of genotype frequencies in the LEP gene between cases and controls. In patients with IRSA, GTCC haplotype in the LEPR gene locus was significantly less frequent than in controls (P = 0.00865, OR 0.45), contrary to ACTC haplotype (P = 0.0087, OR 1.98). Conclusions We showed that genetic variability in the LEPR gene was associated with IRSA, warranting confirmation on a greater number of patients and pathogenesis investigation.