Search Results

1 - 10 of 46 items

  • Keyword: genetic polymorphism x
Clear All Modify Search
Evaluation of Association Between Q192R and L55M Genetic Polymorphisms of PON1 and Serum Paraoxonase-1 Activity in Healthy Individuals, a Meta-Analysis

Abstract

Background and Aims: Several studies have reported the alteration of the paraoxonase 1 (PON1) enzyme activity in various diseases, including diabetes mellitus. The Q192R and L55M are two genetic variations in the coding region of PON1. To evaluate the relationship between these polymorphisms and the alteration in serum paraoxonase activity, the present meta-analysis was carried out. Material and Methods: Eligible studies published before October 2017 was identified in several databases. The paraoxonase activity in subjects with variant alleles of the study polymorphisms were normalized using the activity of the QQ or LL genotypes. The pooled mean effect of alterations in activity level and its 95% confidence intervals (95% CI) was calculated. Results: Thirty-two studies including 11532 healthy participants were used for the present meta-analysis. The paraoxonase activity was increased in the QR and RR genotypes. This elevation was greater among Caucasians than those among Asians and Africans. The activity in the LM and MM genotypes compared with the LL genotype were decreased, this reduction in Caucasians was greater than Africans. Conclusions: At least in part other PON1 polymorphisms and environmental factors may accounts for heterogeneity between studies.

Open access
Genetic Variability of Tumor Necrosis Factor Receptors Type I and II in Lymphoproliferative Diseases in the Serbian Population –

Summary

TNF-alpha and LT-alpha are involved in the pathogenesis of established lymphoproliferative diseases. Both molecules bind to TNFRI and TNFRII. TNFRI is the major mediator of the TNF pro-apoptotic and proliferative effects and TNFRII might enhance these effects. TNF receptors I and II are normally present on hematopoetic cells. TNFR II is characteristic only on immune cells, especially on peripheral leukocytes. Neoplastic B cells and activated B lymphocytes have increased expression of surface TNFR I. In this study, we have analyzed polymorphisms in the TNFRI gene (TNFRI+36A/G SNP) and polymorphism in the TNFRII gene (TNFRII + 676 T/G). All these polymorphisms were studied in patients with chronic lymphocytic leukemia (CLL), patients with non-Hodkin’s lymphoma (NHL) and in healthy controls. The present study was undertaken to investigate the genetic association of these polymorphisms with lymproproliferative disease development.

A total of 68 patients (49-CLL, 19-HNL) were diagnosed at the Clinic of Hematology, Clinical centre Niš, Serbia, using clinical findings and conventional morphological, cytochemical and immunological tests. Genomic DNA was isolated from isolated lymphocytes by proteinase K/phenol/chloroform method, and genotyped for TNFR I (A36G) and TNFR II (T676G) using the PCR-RFLP method.

No significant differences in allele frequencies of TNFR1 polymorphism were found between the patients with lymphoproliferative disease and healthy individuals. In a group of healthy individuals, the study has revealed for the first time significantly higher TNFRI G/G genotype compared to the patients with lymphoproliferative disease (χ22 = 5.66; p = 0.017). Also, we reported the implication of TNFRII T allele in NHL pathogenesis, respectively (χ22 = 10.77; p = 0.001; Mantel-Haenszel: χ22 = 10.64; p = 0.0011).

Our data showed that TNFRII T676G polymorphisms have an important role in NHL pathogenesis but not in CLL patients. A/A polymorphism in TNFRI was not associated with CLL and NHL patients in the Serbian population. Investigated polymorphisms on TNFR genes in leukemic cells of CLL and NHL patients have not showed a correlation with increased proliferation of B lymphocytes and increased expression of TNF R II on B CLL lymphocytes.

Open access
Genetic structure of Hucul and Anglo-Arabian horses at the Tert locus

Abstract

The objective of the study was to identify single nucleotide polymorphism (SNP) genetic markers in the equine TERT gene sequence, which were used to assess the degree of differentiation between Anglo-Arabian and Hucul horses. Polymorphisms were identified by sequencing 30 amplification products representing 18000 bp of TERT sequences. Twenty-seven SNP markers were investigated, which were at genetic equilibrium. Haplotypes and genotypes were determined, and usefulness of polymorphisms for genetic studies was assessed based on minor allele frequency (MAF).

Alleles characteristic of both horse breeds were identified. SNP markers with MAF > 0.18 were

considered suitable for genetic analyses concerning association studies and parentage testing. In

total 26 haplotypes were identified, of which three were common to the investigated horse populations. Twelve haplotypes were found only in Anglo-Arabians and 11 in Hucul horses. Identified

polymorphism of TERT gene might be useful in the search for genetic basis of aging in the Equus

caballus species.

Open access
Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

Abstract

The most important complications of Philadelphianegagive (non BCR-ABL) myeloproliferative neoplasms (MPNs) are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs), platelet glycoproteins (GPs) (Ia/IIa, Ibα, IIb/IIIa and VI), von Willebrand factor (vWF), coagulation factor VII (FVII), β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR) 2.68; 95% confidence interval (95% CI) 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027), (64.7 vs. 44.4 vs. 25%; p = 0.032), respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10) was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31). The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80). The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

Open access
Application of molecular markers in medicinal plant studies

Abstract

The World Health Organization has estimated that more than 80% of the world’s population in developing countries depends primarily on herbal medicine for basic healthcare needs. Approximately two thirds of the 50 000 different medicinal plant species in use are collected from the wild and only 10% of medicinal species used commercially are cultivated. DNA-based molecular markers have utility in the fields like taxonomy, physiology, embryology, genetics, etc. DNA-based techniques have been widely used for authentication of plant species of medicinal importance. The geographical conditions affect the active constituents of the medicinal plant and hence their activity profiles. Many researchers have studied geographical variation at the genetic level. Estimates of genetic diversity are also important in designing crop improvement programmes for the management of germplasm and evolving conservation strategies. The DNA-based molecular marker helps in the improvement of medicinal plant species. DNA markers are more reliable because the genetic information is unique for each species and is independent of age, physiological conditions and environmental factors.

Open access
Association Between Obsessive Compulsive Disorder And Tumor Necrosis Factor-Α Gene –308 (G>A) And –850 (C>T) Polymorphisms In Turkish Children

ABSTRACT

Obsessive compulsive disorder (OCD) is a neurobiological disease characterized with obsessions and compulsions. Obsessive compulsive disorder occurs with an autoimmune mechanism after Group A β hemolytic streptococcus (GABHS) infection. Tumor necrosis factor (TNF) is an important cytokine, as well as having an important role in the apoptosis mechanism of autoimmune diseases. It is expressed by the TNF-α gene. The aim of this study was to examine the relationship between the TNF-α gene promoter region -308 (G>A) and -850 (C>T) polymorphisms and OCD. In this study, ages of the OCD patients and the control group ranged between 4 and 12 years. We studied two patient groups, one included childhood onset OCD patients (n = 49) and the control group was composed of healthy children (n = 58). Patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria and with Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) version. For identifying the polyorphisms, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and polyacrylamide gel electrophoresis (PAGE) methods were used.

For the -308 polymorphism, 45 of 49 OCD patients’ results were completed, and for the -850 polymorphism, 47 of 49 OCD patients’ results were completed. According to our statistical results, there is a positive relationship between OCD and the -308 polymorphism (p <0.001) but no association between OCD and the -850 polymorphism (p = 0.053). There is no positive relationship between antistreptolysin O (ASO) titers and the -308 polymorphism (p = 0.953) but there is an important significance between the -850 polymorphism and ASO (p = 0.010). There is no positive relationship between gender of patients and OCD (p = 0.180) and no positive association between ASO and gender (p = 0.467). According to our results, we hypothesize that we can propose the mutant AA genotype for the -308 polymorphism, and that the mutant CT genotype for the -850 polymorphism may be used as molecular indicators for OCD.

Open access
Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma: introducing a haplotype based approach

Abstract

Background

We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML).

Patients and methods

Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.

Results

Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030).

Conclusions

SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results.

Open access
Characterization of some upland cotton varieties using AFLP and NIR techniques

This study was performed to assess genetic variability and chemical components of five upland cotton (Gossypium hirsutum L.) varieties grown in Syria using AFLP and NIR techniques. These varieties present considerable interest for genetic studies and plant improvement. Twenty-one AFLP PCs primer combinations yielded 1,017 discernible loci of which 495 (50.569%) were polymorphic. Selected markers/primer pairs were ranged between 22 (E-AGA/T-GAA) and 89 (E-GAA/ T-CTT) fragments with an average of 48.429 fragments per primer pair. Marker Index (MI) average for AFLP markers was estimated to be 5.036. Our data revealed that both techniques gave relatively similar results regarding the degree of relatedness among the tested varieties. The pattern generated in NIR technique partially correlated with the other one revealed by AFLP technique. Summarizing all results obtained from NIR and AFLP techniques, we could conclude that chemical structure was relatively reflected in genetic variation among the tested cotton varieties.

Open access
The influence of genetic variability on the risk of developing malignant mesothelioma

Abstract

Background

Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual’s susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.

Patients and methods

In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.

Results

The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83–17.98] and slightly with age, OR 1.10 (95% CI: 1.08–1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59–13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02–2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10–0.77).

Conclusions

Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.

Open access
Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence

Background

Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence.

Patients and methods

In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model.

Results

Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer.

Conclusions

We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.

Open access