Investigation of the relationship between ACAN gene VNTR polymorphism and Alzheimer's disease in Turkish population.

Alzheimer's disease is one of the most common causes of dementia and is a neurodegenerative disease that occurs with memory loss, loss of language, thinking and problem-solving skills. In this study, it was aimed to reveal the relationship between Alzheimer's disease and the variable number tandem repeat (VNTR) polymorphism in the aggrecan (ACAN) gene. Thus, it is thought that it will contribute to enlightenment about disease by contributing to the pathophysiology of Alzheimer's disease. A total of 203 people, including 102 patients diagnosed with Alzheimer's and 101 healthy individuals, were included in the study. Deoxyribonucleic acid (DNA) extraction was performed from the blood samples taken. The variable number tandem repeat (VNTR) polymorphism of the ACAN gene was determined using the Polymerase Chain Reaction (PCR) method. In our study, the 30 R, 31 R and 33 R alleles were the most repetitive alleles in patients and controls. 30 R, 31 R and shorter alleles were more common in patients than in the control group and were found to be statistically significant (p = 0.042). According to our results, 30 R and 31 R alleles of the VNTR polymorphism in the ACAN gene may be associated with Alzheimer's disease. In addition, having less than 30 repeat alleles increases the risk of the disease by 2,202 times. Our study is the first to investigate the relationship between ACAN gene VNTR polymorphism and Alzheimer's disease. Further studies are needed to definitively relate it.

Association between Alzheimer's disease, MAPT gene mutation and some biochemical biomarkers.

Alzheimer's Disease (AD) is a multifactorial neurodegenerative disease and there is still no definitive treatment today. Early diagnosis of the disease is important, but there are almost no biomarkers that can be used in early diagnosis. The cerebrospinal fluid used in the diagnosis of the disease is not sufficient and is very difficult to obtain. Therefore, blood biomarkers that are less costly, less invasive, easily accessible, and can be used in long-term studies would be a better alternative. The aim of this study is to determine the relationship between Alzheimer's Disease and P301L MAPT gene mutation, homocysteine, folate and uric acid. 101 Alzheimer's patients and 101 healthy individuals were included in this study. Mutation analysis was performed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method with blood samples taken from the subjects. There was no significant difference between the patient and control groups in terms of homocysteine (p = 0.771), folate (p = 0.366) and uric acid (p = 0.860). When the genotypes were compared between the patient and control groups in terms of MAPT gene mutation (P301L), no statistically significant difference was detected (p = 0.081). There are very few studies in the literature investigating the relationship between Alzheimer's disease and P301L MAPT gene mutation. Additionally, there is no study investigating the relationship between Alzheimer's disease and homocysteine, folate, uric acid and P301L MAPT mutation in the Turkish population. We believe that this study has shed light on future studies.

Identification of the effects of pathogenic genetic variations of human CYP2C9 and CYP2D6: an in silico approach.

Genetic variations in the human cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily D member 6 (CYP2D6) genes may affect drug metabolism and lead to alterations in phenotypes. Genetic variations are associated with toxicity, adverse drug reactions, inefficient treatment. Various in silico tools were combined to investigate the deleterious effects of missense non-synonymous single nucleotide polymorphisms (nsSNPs) of the human CYP2C9 and CYP2D6. The structural and functional effects of the high-risk non-synonymous SNPs in the human CYP2C9 and CYP2D6 were predicted by numerous computational mutation analysis methods. Out of 24 pathogenic missense SNPs in the CYP2C9, 22 nsSNPs had a decreasing effect on protein stability and 13 SNPs were showed to be located at conserved positions. Out of 27 high-risk deleterious non-synonymous SNPs in the human CYP2D6, 21 SNPs decreased protein stability and 16 nsSNPs were predicted to be positioned at conserved regions. Our present study suggests that the identified functional SNPs may affect drug metabolism associated with CYP2C9 and CYP2D6 enzymes.

Association between dopamine transporter gene (DAT1/SLC6A3) variants and infertility in the Turkish females.

OBJECTIVE: Worldwide, approximately 10-15% of couples is affected by infertility and infertility is associated with disturbances in female and/or male reproductive systems. The aim of the current study is to investigate the relationship between DAT1 (SLC6A3) VNTR polymorphism with female infertility. METHODS: Genomic DNA extractions were performed in 98 fertile and 90 infertile females, 3' untranslated region (3' UTR) variable number tandem repeat (VNTR) polymorphism of DAT1/SLC6A3 was determined by the use of Polymerase Chain Reaction (PCR) method. RESULTS: It has been demonstrated that there was no statistically significant difference between female infertile and fertile groups in the terms of DAT1 genotypes (p > .05). Moreover, there was no significant difference regarding the frequencies of 9R and 10R alleles in infertile and fertile groups (p > .05). CONCLUSION: This is the first study for investigating the relationship between DAT1/SLC6A3 gene polymorphism and infertility in females. Our study contributes to the growing awareness of the relationship between dopaminergic system and female infertility despite no significant differences were reported between infertile females and corresponding fertile subjects in DAT1/SLC6A3 gene.

Are dopaminergic genotypes risk factors for eating behavior and obesity in adults?

Dopamine (DA) is the main modulator of the brain reward system and significantly regulates food intake. The idea that obesity is a neurobiological disease rather than a metabolic disorder, is the basis of the study. Changes in dopamine neurotransmission affect the brain reward system in a direct way. Furthermore, changes in the reward system influence the eating behavior in human. The enzymes monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) terminate the DA function by metabolizing it. In our study, the control group which included 214 individuals and 234 subjects with obesity were investigated for MAOA-u VNTR and COMT (rs4680) polymorphisms. In our study, statistical analysis has showed that in control group Val/Met COMT genotype was significantly higher compared with the patient group (p=0.04). When the groups were compared in terms of eating behavior, the number of the subjects who ate for reward was significantly higher in patient group (p=0.03). Our findings demonstrated that eating behavior might have an effect on obesity and dopaminergic polymorphisms could be risk factors for the development of obesity in Turkish population.