[The analysis of association between ENPP1 K121Q polymorphism and risk factors of type 2 diabetes mellitus in ukrainian population].

OBJECTIVE: Introduction: More than 100 genes have been described associations between single nucleotide polymorphisms and type 2 diabetes mellitus (T2DM). Among these candidate genes, Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1), is located on the long arm of chromosome 6 (6q23.2) and encodes for a protein which is one of the factors determining the insulin sensitivity. An allelic polymorphism in exon 4 of ENPP1 (rs1044498) has been designated K121Q and widely investigated in T2DM in different populations. The aim: To analyze the association between ENPP1 K121Q polymorphism with the risk factors of type 2 diabetes mellitus in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 317 patients with type 2 diabetes mellitus and 302 controls was used for analysis. ENPP1 K121Q genotyping was performed using PCR-RFLP method. RESULTS: Results: Our results revealed that ratio of K/K homozygotes, K/Q heterozygotes and Q/Q homozygotes between case and control groups was significantly different (59.3%, 34.1%, 6.6% vs 67.9%, 28.5%, 3.6%, P = 0.05). Method of binary logistic regression shown that a reliable relationship was established in the general group for KQ/QQ vs K/K genetic model (P = 0.027). It was shown that in carriers of the minor Q-allele, the risk of T2DM is 1.4x higher than in homozygotes in the main K-allele (95% CI = 1.043-2.016). After adjusting for age, sex, smoking habit, BMI, obesity and the presence of hypertension, the reliability of these results persisted (P = 0.026). CONCLUSION: Conclusions: ENPP1 K121Q polymorphism is associated with T2DM in Ukrainian population. In carriers of the minor Q-allele the risk of T2DM is 1.4x higher than in homozygotes in the main K-allele. The risk increases in patients with BMI ≥ 25 kg/m2.

Positive Association between EDN1 rs5370 (Lys198Asn) Polymorphism and Large Artery Stroke in a Ukrainian Population.

There are a lot of convincing evidences about the involvement of endothelin pathway proteins in the pathogenesis of atherosclerosis and its fatal complications. In this study, the analysis of a possible association between EDN1 rs5370 and EDNRA rs5335 gene polymorphisms and the risk of large artery stroke (LAS) in a Ukrainian population was conducted. 200 LAS patients and 200 unrelated controls were enrolled in a case-control study. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used for SNP genotyping. Our results revealed that EDN1 rs5370 polymorphism was associated with LAS development both before and after adjustment for atherosclerosis risk factors (sex, age, body mass index, arterial hypertension, type 2 diabetes mellitus, and smoking). The risk for a LAS incident in rs5370-T allele carriers was 1.6 times higher (CI = 1.066-2.403; P = 0.020) than in subjects with the GG genotype. No link between EDNRA rs5335 and LAS risk in a Ukrainian population was found. The present study indicated that EDN1 rs5370, but not EDNRA rs5335, can be the strong genetic predictor for LAS development in a Ukrainian population.

[The association between enpp1 rs997509 polymorphism and type 2 diabetes mellitus development in ukrainian population].

OBJECTIVE: Introduction: Genome-Wide Association Studies have identified a large number of polymorphic loci associated with type 2 diabetes mellitus (T2DM). Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) gene is one of the candidate genes which have primary importance in T2DM development. Several studies revealed the association between ENPP1 polymorphisms, including rs997509, and T2DM, obesity, insulin resistance and metabolic syndrome in different populations. The aim: To test the association between ENPP1 rs997509 polymorphism and T2DM development in patients with different risk factors in the Ukrainian population. PATIENTS AND METHODS: Materials and methods: Venous blood of 317 unrelated T2DM patients and 302 healthy volunteers was used for analysis. ENPP1 rs997509 genotyping was performed using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. RESULTS: Results: Our results revealed that ratio of C/C homozygotes, C/T heterozygotes and T/T homozygotes between case and control groups was significantly different (89.0 % , 11.0%, 0 % vs 94.4 %, 5.6 %, 0 %, P = 0.015). It was shown that risk of T2DM development in T allele carriers is significantly higher compared to C/C homozygotes (OR = 2.086; P= 0.027). Herewith the risk increased in heterozygotes with BMI ≥ 25 kg/m2 (OR = 2.223, P=0.031) and obesity (OR = 3.230; P = 0.023). CONCLUSION: Conclusions: ENPP1 rs997509 polymorphism is associated with T2DM development in Ukrainian population.

The histological and electron microscopic study of the parotid salivary gland in dehydrated rats of different ages.

OBJECTIVE: Introduction: Water-salt metabolism disorders is one of the main factor of salivary gland pathology development. The aim: To study the morphological structure of the parotid salivary gland of young, mature and old rats at micro- and ultrastructural levels under water deprivation. PATIENTS AND METHODS: Materials and methods: The experiment was carried out on thirty six laboratory male rats of different ages (young, mature and old). The rats of the control group received normal volume of drinking water. The rats of the experimental group were deprived of water for 6 days. Light microscope "OLYMPUS" and transmission electron microscope JEM-1230, (JEOL, Japan) were used for structural analysis. RESULTS: Results: Obtained results revealed increasing numbers of vacuoles in the serous cells, the enlarged cisterns of endoplasmic reticulum and Golgi apparatus tubules, the condensed chromatin and the nuclei with significant invaginations in parotid gland of the rats of all age groups. The area of the acinuses more changed in young rats, the decrease was 34.61 % (P = 0.007). The internal diameter of capillaries most decreased in the dehydrated old rats by 23.76 % (P = 0.009) in comparison with all study groups. CONCLUSION: Conclusions: Water deprivation brings about the structure changes of the parotid gland at micro- and ultrastructural levels the intensity of which depends on the age of animals. The most dramatic changes have occurred in young and old rats.

G-1639A but Not C1173T VKORC1 Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population.

Vitamin K epoxide reductase complex subunit 1 (VKORC1) is integral 163-amino acid long transmembrane protein which mediates recycling of vitamin K 2,3-epoxide to vitamin K hydroquinone and it is necessary for activation of vitamin K-dependent proteins (VKDPs). Herein, the association between G-1639A (rs9923231) and C1173T (rs9934438) single-nucleotide polymorphisms (SNPs) of the VKORC1 gene and ischemic stroke (IS) was tested in Ukrainian population. Genotyping was performed in 170 IS patients and 124 control subjects (total 294 DNA samples) using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. Our data showed that G-1639A but not C1173T polymorphism was related to IS, regardless of adjustment for age, sex, body mass index, smoking status, and arterial hypertension. The risk for IS in -1639A allele carriers (OR = 2.138, P = 0.015) was higher than in individuals with G/G genotype. Haplotype analysis demonstrated that -1639G/1173T and -1639A/1173C were related to increased risk for IS (OR = 3.813, P = 0.010, and OR = 2.189, P = 0.011, resp.), while -1639G/1173C was a protective factor for IS (OR = 0.548, P < 0.001). Obtained results suggested that -1639A allele can be a possible genetic risk factor for IS in Ukrainian population.