Genetic Aspect of Headache

Headache is a multifactorial disease and the genetic basis is not clear yet. We review recent findings about molecular basis of subtypes of headache. The fundamentals of molecular genetics and the recent advances in this area are important for clinicians to understand the pathogenesis of the disorder. Recent studies provide a foundation for critical appraisal of the literature, unprecedented insights and reveal promising treatment targets for future drug development. This chapter provides an overview of molecular genetics, epigenetic and genome‐wide association studies on headache. In summary, we try to explain the state‐of‐the‐art molecular basis of headache and the possible future direction in this field of research studies. According to recent studies the main types of are evaluative, exploratory about molecular basis of headache. In recent years, new studies have been designed to provide an update and understanding of the modern day genetics, the advances in genetic research and methods and a basis for understanding the strategy by which advances in molecular genetics can be applied for understanding complex polygenetic diseases such as migraine

Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue.Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis.Study Design: Case-control study.Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction.Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022).Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis

Homozygous Ala65Pro Mutation with V89L Polymorphism in SRD5A2 Deficiency

Objective: Deficiency of steroid 5-alpha reductase type 2 (5?RD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5?RD2 deficiency. Methods: 5?RD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5?RD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common.Objective: Deficiency of steroid 5-alpha reductase type 2 (5?RD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5?RD2 deficiency. Methods: 5?RD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5?RD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common

A Study of the Impact of Death Receptor 4 (DR4) Gene Polymorphisms in Alzheimer"s Disease

Background: Excessive apoptosis is believed to play a role in many degenerative and non-degenerative neurological diseases including Alzheimer’s disease (AD). Much recent data suggest that apoptotic mechanisms may represent the missing link between Aβ deposition and proteolysis of tau protein. However, there is emerging evidence that apoptotic mechanisms may play a role in Alzheimer’s Disease pathogenesis in the absence of overt apoptosis. TNF-related apoptosis inducing ligand receptor 1 (Death Receptor 4, DR4) might impair the apoptotic signal transduction and lead to dysregulation of the homeostasis between cell survival and cell death. Aims: The aim of our study was to further investigate the relationship between genetic variants of DR4 and Alzheimer’s Disease. Study Design: Case control study. Methods: Sixty-eight patients with AD were included in the study. The control group comprised 72 subjects without signs of neurodegenerative diseases, as evidenced by the examination.DNA was extracted from whole blood using the salting-out procedure. Genotypes were identified by restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) products. Results: We observed significant differences in the genotypic distribution of the rs6557634 polymorphism in AD patients compared with controls (p0.05) and the DR4 rs20576 polymorphism (p>0.05). According to haplotype analysis of the DR4 gene for rs6557634, rs20575 and rs20576 polymorphisms, GCA and GCC haplotypes might be a risk factor for AD. Also, we have shown that ACA, GGC and GGA haplotypes might be protective factors against AD. Conclusion: The present results indicate for the first time the possible contribution of the DR4 gene rs6557634, rs20575, rs20576 polymorphisms in Alzheimer’s Disease, which may influence susceptibility to Alzheimer’s Disease

Exploration of Potential miRNA Biomarkers and Prediction for Ovarian Cancer Using Artificial Intelligence

Ovarian cancer is the second most dangerous gynecologic cancer with a high mortality rate. The classification of gene expression data from high-dimensional and small-sample gene expression data is a challenging task. The discovery of miRNAs, a small non-coding RNA with 18-25 nucleotides in length that regulates gene expression, has revealed the existence of a new array for regulation of genes and has been reported as playing a serious role in cancer. By using LASSO and Elastic Net as embedded algorithms of feature selection techniques, the present study identified 10 miRNAs that were regulated in ovarian serum cancer samples compared to non-cancer samples in public available dataset GSE106817: hsa-miR-5100, hsa-miR-6800-5p, hsa-miR-1233-5p, hsa-miR-4532, hsa-miR-4783-3p, hsa-miR-4787-3p, hsa-miR-1228-5p, hsa-miR-1290, hsa-miR-3184-5p, and hsa-miR-320b. Further, we implemented state-of-the-art machine learning classifiers, such as logistic regression, random forest, artificial neural network, XGBoost, and decision trees to build clinical prediction models. Next, the diagnostic performance of these models with identified miRNAs was evaluated in the internal (GSE106817) and external validation dataset (GSE113486) by ROC analysis. The results showed that first four prediction models consistently yielded an AUC of 100%. Our findings provide significant evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer

G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk

The G-protein-coupled estrogen receptor (GPR30, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants’ leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer’s exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population.

Migren Hastalarında CHRNA4 Gen Polimorfizmilerinin, Oksidatif DNA Hasarı ve Oksidatif Stres Markır Seviyelerinin Analizi

Amaç: Migren, oldukça karmaşık bir genetik etyopatogenezi olan primer başağrısı sendromudur. Migrenin altında yatan mekanizmalar henüz net olarak aydınlatılamamıştır. Çalışmamızın amacı, CHRNA4 geni polimorfizmleri ile migren arasındaki ilişkinin araştırılması ve migren hastalarının plazmalarında 8-oxo2dG ve AOPP düzeylerinin tespiti ile oksidatif DNA hasarı ve oksidatif stresin belirlenmesidir. Method: Çalışmamızda, migren hastaları (n = 79) ve ilişkisiz sağlıklı bireylerden (n = 68) DNA elde edildi. CHRNA4 geni rs1044393 ve rs1044394 polimorfizmlerine ait allel ve genotipler PCR ve RFLP yöntemleri ile belirlendi. Ayrıca, migrenli hastaların plazmasında 8- oxo2dG ve AOPP düzeyleri ölçüldü. Bulgular: Çalışmamızın sonucunda, aurasız migren hastaları ile CHRNA4 geni rs1044394 polimorfizmi arasında anlamlı bir ilişki tespit edildi (p <0.05). Ayrıca, CHRNA4 geni rs1044394 polimorfizmi ile sigara kullanan migren hastaları arasında anlamlı bir ilişki olduğu belirlendi (p <0.05). İlginç bir sonuç olarak, sağlıklı kontrollere oranla migren hastalarında 8- oxo2dG düzeyinin daha düşük olduğu tespit edildi. (p <0.05). Sonuç: Verilerimize göre, CHRNA4 geni migren hastalığı için önemli olabilir. Ayrıca, ilaç tedavisi alan migrenli hastaların plazmasındaki 8-oxo2dG düzeyinde azalma olabileceği belirlenmiştir Bu durum, migrendeki ilaç tedavisinin oksidatif stresi azaltıyor olabileceğini göstermektedir.Aim: Migraine is a primary headache syndrome which has been a genetic factor in quite complex etiopathogenesis. The mechanisms underlying the migraine have not been clearly enlightened. The aim of our study is to investigate the relationship between polymorphisms of CHRNA4 gene and migraine and determined to oxidative DNA damage and oxidative stress with detection of 8-oxo2dG and AOPP levels in plasma of patients with migraine. Methods: In our study, DNA was obtained from migraine patients (n=79) and unrelated healthy persons (n=68). Alleles and genotypes of CHRNA4 gene polymorphisms (rs1044394, rs1044393) were determined with PCR and RFLP methods. Also, 8-oxo2dG and AOPP levels were measured in plasma of migraine patients. Results: As a result, we were found a significant relationship between rs1044394 polymorphism of CHRNA4 gene and migraine patients without aura (p <0.05). Also, it was shown a significant association between rs1044394 polymorphism of CHRNA4 gene and smoker migraine patients (p <0.05). As an interesting, 8-oxo2dG levels in migraine patients were determinate significantly lower than healthy controls (p <0.05). Conclusions: According to our results, CHRNA4 gene may be important for migraine disease. Also, 8-oxo2dG levels in plasma of patients with migraine who have take medicine treatment might be decreased. This situation may show that drug therapy for migraine may reduce oxidative stress

Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model

Background & objectives: Vaginal atrophy is characterized by thinning of vaginal epithelial layers and decreased local blood flow. We aimed to evaluate the regenerative effects of Adipose derived mesenchymal stem cells (ADMSC) and Bone marrow derived mesenchymal stem cells (BMDSC) on vaginal atrophy in rat menopause model