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The Vascular Endothelial Growth Factor (VEGF) family of proteins exerts an essential role in vascular development. Variances in the expression of the VEGF gene have been associated with cancer, inflammatory diseases, pregnancy disorders. A single nucleotide polymorphism (SNP) in the 3'-untranslated region (C936T) is responsible for the under-expression of the gene. Our aim was to determine for the first time in our country the frequency of the C936T SNP in a Romanian population group and to compare its general distribution with the data obtained in a group of recurrent spontaneous abortion (RSA) cases. Using the molecular genetics technique PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism), we genotyped 163 Romanian unrelated healthy subjects who consented on participating in the screening for the VEGF C936T polymorphism and an additional number of 113 patients with history of RSA. The screening revealed a genotype distribution of 3.1% TT homozygotes, 23.9% heterozygotes and 73% CC homozygotes reflecting a frequency of 15.0% of the mutant allele T and 85.0% of the wild-type allele C. In comparison with the general population a slight higher frequency of 15.9% for the mutant allele was found in the RSA group. Comparing our findings with the ones obtained in other ethnic groups, no specific pattern can be drown for the variance of this polymorphism, a fact explained by the still dispersed studies on the epidemiological aspects of this SNP. Although there is little difference between the screening results and those concerning the RSA group, a future prospective of this approach is the effectuation of a case-control study in order to obtain specific information. [ABSTRACT FROM AUTHOR]

Background. The folate pathway consists of a complex chain of biochemical reactions essential for the cellular function. Within this pathway C1-THF synthase (C-1-tetrahydrofolate synthase) coded by the MTHFD1 gene is crucial for the conversion of homocysteine to methionine, as well as purine and pyrimidine synthesis. The MTHFD1 G1958A variant could alter the enzyme's normal activity which may further modify this metabolic pathway. Objectives. To explore the possible association of the MTHFD1 G1958A polymorphism and idiopathic male infertility. Patients and Methods. Sixty-six male Romanian patients with idiopathic infertility and 67 fertile Romanian men were genotyped for the MTHFD1 G1958A variant, using the polymerase chain reaction — restriction fragment length polymorphism technique (PCR-RFLP). Results. The 1958A allele had a frequency of 52.27% in the male infertility group, and 45.52% in controls. The comparative analysis between patients and controls genotypes distribution revealed the 1958AA homozygous genotype was more frequent in the male infertility group than in controls (OR = 2.139, p-value = 0.07) Conclusions. We have found that the variant homozygous genotype might represent a genetic risk factor for idiopathic infertility in our study groups. [ABSTRACT FROM AUTHOR]

The periodontal disease is one of the most important diseases in the oral pathology with major esthetical and functional impact at the individual level and also with important implications at the medical and social scale. As a multifactorial disease, involving also an inflammatory condition, in which important roles are being held by both genetic and non-genetic factors, the periodontal disease is and has been intensely studied with the purpose of detecting the risk and etiologic factors that drive it. The objective of the present study is to evaluate a common polymorphism (-799C/T) in the promoter region of the gene encoding the matrixmetaloproteinase 8, as a possible genetic risk factor for periodontal disease. In this scenario we have conducted a case-control study that has involved a case group composed of 39 patients with periodontal disease, the chronic or aggressive form and a control group of 33 subjects without periodontal disease. The genotype analysis of the -799 C/T polymorphism was performed through molecular genetic techniques, using DNA extracted out of peripheral blood samples. Considering the CT and TT genotypes, the statistic interpretation of the data obtained in the two compared groups shows a weak association (OR 1.9, 95% CI 0.72-4.95) without reaching statistical significance (p=0.14). Nevertheless, the comparison of the group of patients presenting chronic periodontal disease with the control group reveals the fact that, for this form of the disease, the studied polymorphism can be considered as risk factor (OR 3.11 95% CI 1.02 - 9.41, p=0.03), conclusion not applying, however, for the aggressive form of the disease (OR 0.90 95% CI 0.25-3.27, p=0.57). To our knowledge, this study represents the first association study between MMP8 -799C/T polymorphism and periodontal disease in Romania, representing a first step in the identification of some possible genetic risk variants in our population. The knowledge of these variants would give important information on the genetic risk factors as well as their possible associations with environmental factors that might be eventually acting in synergy in the etiology and progression of the periodontal disease. [ABSTRACT FROM AUTHOR]

β-thalassaemia is caused by mutations that result in the reduced or non-production of β-globin chains. Around 200 such mutations have been identified so far. Most homozygotes suffer from a severe syndrome and require regular blood transfusions to survive. This makes β-thalassaemia one of the most significant single gene disorders globally. The aim of our study was to determine which mutation in the β-globin encoding gene is responsible for the occurrence of β-thalassaemia in a group of 37 Romanian patients. In order to assess which mutation in the β-globin gene lead to the clinically diagnosed occurrence of β-thalassaemia in our Romanian group we performed genetics analysis by means of molecular genetics techniques, respectively ARMS -PCR (Amplification Refractory Mutation System - Polymerase Chain Reaction) by amplifying both the mutant and normal allele. We analyzed if the following 5 mutations: IVS I-110 (G→A), cd 39 (C→T), IVS II-745 (C→G), IVS I-1 (G→A) and -87 (C→G) are responsible for this form of pathology. Also, we investigated the possible phenotype variation due to mutations in the HFE gene. We obtained a number of 5 heterozygotes for the IVS II-745 (C→G) mutation and 5 heterozygotes for the IVS I-110 (G→A) mutation and no compound heterozygote or homozygote for any of the HFE mutations. Because β-thalassaemia is a disorder which has a strong degree of genetic heterogeneity more powerful methods must be used in order to perform a complete molecular diagnosis, such as β-globin gene sequencing. The early detection, prevention and prophylaxis of this form of pathology must be taken into account by all national health systems. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp) is an ATP-dependent efflux pump which has great importance in absorption and elimination of several important drugs. The MDR1 (Multiple Drug Resistance 1) gene, which codes for P-gp, has been shown to be polymorphic. Among the multiple variants of the MDR1 gene, a silent polymorphism, namely C3435T, has been shown to modulate the metabolization and thus the therapeutic response to the drug substrates for P-gp. Our study was an attempt to evaluate the distribution of the MDR1 C3435T polymorphism in the Romanian population, as there were no such data reported on our population. We screened for the C3435T polymorphism 102 healthy Romanian individuals, using a PCR-RFLP assay. We found 25 (24.5%) homozygous individuals for the C allele, 55 (54%) heterozygous individuals, while 22 (21.5%) individuals were homozygous for the T allele. Thus, the alleles frequencies in the group studied were: 51% for the C allele and 49% for the T allele. Overall, the MDR1 C3435T polymorphism had a similar distribution in the Romanian population as in other Caucasian populations. Our study brings important pharmacogenomic data regarding the Romanian population and it represents meanwhile a step towards a personalized drug therapy in our country. Further studies regarding different other polymorphism in genes coding proteins involved in drugs metabolism are needed on the Romanian population, in order to obtain a more complex pharmacogenomic profile of our population. [ABSTRACT FROM AUTHOR]

Low dietary folate intake has been blamed for many pathologies including cancers, thrombophilia, congenital anomalies (e.g. neural tube defects) and recurrent spontaneous abortions (RSA). An important biological function of folates, which is closely related to homocysteine levels, is to provide methyl groups, which are essential for DNA methylation reactions and for deoxynucleotide synthesis. There are many enzymes involved in the folate-homocysteine metabolic pathway and some polymorphisms in the genes coding for these enzymes can lead to an inappropriate activity of their corresponding enzymes. One of the key enzymes in the homocysteine metabolism is the methionine synthase reductase (MTRR) which catalyzes the regeneration of methylcobalamin, a cofactor for another important enzyme named methionine synthase (MTR). We hypothesized that the 66G>A substitution of the MTRR gene could be associated with an increased risk for recurrent spontaneous abortion (RSA). In a case-control study comprising 131 women with RSA and 131 healthy fertile women without any history of spontaneous abortion we genotyped MTRR 66G>A polymorphism by PCR-RFLP methods. We found that the MTRR variant GA and GA/AA genotypes were associated with a significant risk for RSA: odds ratio (OR), 2.00 ; 95% confidence interval (95% CI), 1.21-3.29 for GA and OR, 2.10; 95% CI, 1.28-3.43 for GA+AA compared with the GG genotype. In conclusion, our data provide evidence that there could be an association between MTRR 66G>A variant and RSA risk. [ABSTRACT FROM AUTHOR]