An Association between MPO-463 G/A Polymorphism and Type 2 Diabetes

Myeloperoxidase (MPO) is an enzyme which is a member of the haem-peroxidase superfamily and plays a role in production of reactive oxygen species. The most common polymorphism in the promoter region of MPO gene is -463 G/A. It was shown that carrying the GG genotype means increased activity of the gene approximately 2-3-fold compared to GA and AA genotypes. It was found that hyperglycaemia, modified oxidized proteins and increased advanced glycosylated end products (AGE) are related to oxidative stress in diabetes. Under the hyperglycaemic conditions, production of reactive oxygen radical is elevated in smooth muscle endothelial cells, mesengial and tubular endothelial cells. Especially, elevated lipid oxidation plays an important role in pathogenesis of diabetic complications such as cardiovascular complications. We examined the MPO -463 G/A polymorphism by using the PCR-RFLP method in 145 type 2 diabetic patients and 151 healthy controls. We observed that the AA genotype and A allele were protective variants against type 2 diabetes and the GG genotype was a risk factor for diabetes. While we studied the relationship between genotypes and biochemical parameters, we found that patients with the A allele had decreased serum cholesterol, triglyceride, VLDL levels and body mass index. We suggest that the MPO gene has an important role in pathogenesis of type 2 diabetes because of the increased frequency of GG genotype, which is related to increased activity and oxidant capacity of MPO in the patients

Analysis of toll-like receptor 9 gene polymorphisms in sepsis

Aim: To analyze the effect of TLR-9 (-1486 T>C) and TLR-9 (C>T) gene polymorphisms both at TLR-9 levels and together with their sepsis parameters. In this regard, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used in order to detect TLR-9 gene polymorphisms, whereas the ELISA technique was used to analyze TLR-9 serum levels in 80 sepsis patients and 100 healthy individuals. Materials and Methods: The study group consisted of 80 patients with a diagnosis of sepsis and 100 healthy individuals. TLR-9 C>T polymorphism was identified by PCR-RFLP. Results: There was no substantial difference observed between sepsis and control groups in terms of TLR-9 (-1486 T>C) and TLR-9 (C>T) genotype and allele distribution. When serum TLR-9 levels were compared to TLR-9 (-1486 T>C) and TLR-9 (C>T) genotype and allele distribution, there was a statistically substantial decrease in TLR-9 serum levels of both TLR-9 (-1486 T>C) TT and TLR-9 (C>T) TT individuals in the sepsis group (p=0.011 and p=0.036, respectively). Conclusion: There is no relation between sepsis and both TLR-9 (C>T) and TLR-9(-1486 T>C) polymorphisms; however, there is a relation between sepsis and decreased serum TLR-9 levels of both TLR-9 (-1486 T>C) TT and TLR-9 (C>T) TT polymorphisms due to sepsis-associated immunosuppression

The effects of Advanced Glycation End Products (RAGE)-374T/A and Gly82Ser variants and soluble-RAGE levels to obesity in children

In recent years, studies related to advanced glycation end products (AGE) and their interaction with their receptors (RAGE) have advanced our knowledge of the roles of these molecules in different diseases. However, studies concerning AGE-RAGE interaction in obesity are limited and the results are conflicting. RAGE gene is located on 6p21.3, has several polymorphic sites including -374T/A, a functional polymorphism in the promoter region, and Gly82Ser, present within the ligand-binding domain. In the present study, the determination of possible risks in the development of obesity according to RAGE polymorhisms and plasma levels of RAGE (sRAGE) was aimed. 87 obese and 78 healthy children were included in this study. Genomic DNA was isolated with salting-out procedure. RAGE polymorphisms were analyzed by PCR based techniques. In contrast to Gly82Ser, -374T/A allelic and genotypic frequencies were not different between study groups. Ser(SerSer+GlySer genotype) allele frequency was higher in obese cases than controls (74.20%-> 25.80%, OR: 2.573,95% CI:1.789-3.699; p 87.00 +/- 1.16; p=0.025) and HDL-C (46.14 +/- 2.75 -> 39.84 +/- 1.82;p=0.057) levels were higher than TT genotype carriers. As for Gly82Ser polymorphism, HDL-C (p=0.004) and FT4 (p=0.020) levels were different in obese cases, the order was SerSer>GlySer>GlyGly for HDL-C, and opposite for FT4. Besides, Ser carriers had lower insulin (p=0.038) and homa-IR (p=0.081) levels than GG genotype. sRAGE levels were different between obese and control seperately or in combination with RAGE polymorphisms (pTA>AA for -374T/A and SerSer>GlyGly>GlySer for Gly82Ser. According to our results SerSer genotype could have significant effects on sRAGE levels, and increased sRAGE levels and Gly82Ser polymorphism either combinatorially or seperately increased the propensity towards obesity

Investigation of RASSF4 gene in head and neck cancers

Objectives RASSF gene family can inhibit the growth of RAS oncogene. This gene family is suggested to have a role in cell cycle control, apoptosis, cell migration, and mitosis control. This study evaluated RASSF4 gene expression levels, SNPs and serum levels in tissues dissected from both healthy individuals and patients diagnosed with head, and neck cancer. Methods RASSF4 gene expression levels were determined using the RT-PCR. Serum levels of RASSF4 were tested using the Enzyme-Linked Immuno Sorbent Assay technique in study groups. RASSF4 rs7896801 and rs884879 genotypes were identified using by the RT-PCR. Results No statistical difference was observed between study groups according to RASSF4 gene expression levels. According to SNP results, rs7896801 revealed a 2.4 fold increase of G-allele presence in patients (p=0.015). The increase in the presence of AA genotype was statistically significant for the control group (p=0.015). Distribution of genotypes and alleles for rs884879 showed a 2.2 fold increase in CC genotype for healthy group (p=0.031) however, the presence of T allele showed a significant increase in the patients (p=0.048). Conclusions We suggest that this study will play a pioneering role for the next studies on RASSF4 gene, especially on SNPs