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The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54Males/59Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P < 0.05) and lower content of arachidonic acid in plasma phosphatidylcholine (PC) (P = 0.052), lower index of Δ5 desaturation (P < 0.01) and unsaturation index (UI) (P < 0.001). In contrast, DD patients had higher concentrations of plasma glucose, insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.

Pancreatic cancer (PC) is one of the most frequent gastrointestinal malignancies with extremely poor prognosis. In spite of a relative low incidence of PC, in comparison with other cancers, PC is the fourth leading cause of cancer death in USA in both sexes. The available data clearly suggest that diabetes mellitus (DM) can be both a long-standing cause of PC and an early manifestation of the disease. Besides of DM, insulin resistance and high insulin levels are linked as well with increased cancer risk, including PC. The variable number of tandem repeats (VNTR) locus upstream of the insulin gene (INS) regulates insulin expression and has been associated with susceptibility to many diseases including DM. It is known that there is nearly complete linkage disequilibrium of the insulin variable tandem of repeats (INS-VNTR) alleles I/III with neighboring -23 HphI A/T single nucleotide polymorphism (SNP) in Caucasians. Therefore, we have studied the association between SNP of -23HphI in promoter of INS with PC, DM Type 2 (2TDM) and healthy controls. In this study we investigated 153 subjects (86 M/67 F); 51 patients with newly-diagnosed PC (31 M/20 F), 45 patients with 2TDM (29 M/16 F) and 57 healthy control subjects (26 M/31 F). The polymorphism of -23HphI (A/T) in the promoter of INS was determined by the combination of polymerase chain reaction (PCR) with the restriction fragment length polymorphism (RFLP) methods. The results obtained by the PCR-RFLP analyses of SNP -23HphI were confirmed by a direct studied locus sequencing of the genomic DNA. The frequency of abnormal glucose metabolism (both DM and impaired fasting glucose) was 88 % (45/51) in PC group. The AA genotype in SNP -23HphI was more prevalent (67 % vs. 47 %; P

Mutations in troponin T (TNNT2) gene represent the important part of currently identified disease-causing mutations in hypertrophic (HCM) and dilated (DCM) cardiomyopathy. The aim of this study was to analyze TNNT2 gene exons in patients with HCM and DCM diagnosis to improve diagnostic and genetic consultancy in affected families. All 15 exons and their flanking regions of the TNNT2 gene were analyzed by DNA sequence analysis in 174 patients with HCM and DCM diagnosis. We identified genetic variations in TNNT2 exon regions in 56 patients and genetic variations in TNNT2 intron regions in 164 patients. Two patients were found to carry unique mutations in the TNNT2 gene. Limited genetic screening analysis is not suitable for routine testing of disease-causing mutations in patients with HCM and DCM as only individual mutation-positive cases may be identified. Therefore, this approach cannot be recommended for daily clinical practice even though, due to financial constraints, it currently represents the only available strategy in a majority of cardio-centers.