Elif Funda Sener

Endothelial Nitric Oxide Synthase Gene Expression Is Associated with Hypertension in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Early occurrence of hypertension is the prominent feature of autosomal dominant polycystic kidney disease (ADPKD). The role of angiotensin-converting enzyme (ACE) gene polymorphism and endothelial nitric oxide synthase (eNOS) gene polymorphism in the clinical course of ADPKD is not well understood. However, data about the expression of these genes are lacking. Thus, we aimed to investigate the polymorphisms and expressions of both the ACE and eNOS genes that affect hypertension in ADPKD. Methods: Whole blood samples were obtained from all participants. ACE and eNOS gene polymorphisms and their expressions were analyzed in 78 ADPKD patients and 30 controls. Gene expressions were assessed by quantitative real-time PCR. Twenty-four-hour blood pressure monitoring was performed for the diagnosis of hypertension in all study participants. Results:eNOS expression and the estimated glomerular filtration rate were found to be significantly higher in ADPKD patients without hypertension than in those with hypertension. Each unit of increase in eNOS expression led to a 0.88-fold decrease (95% CI: 0.80-0.96) in the risk of hypertension in multiple logistic regression analysis. Conclusions:eNOS gene expression is independently predictive of hypertension in the ADPKD population. This study showed, for the first time, a novel link between eNOS gene expression and hypertension in ADPKD.

Recent Advances in Autism Spectrum Disorders: Applications of Whole Exome Sequencing Technology

Autism spectrum disorders (ASD) is characterized by three core symptoms with impaired reciprocal social interaction and communication, a pattern of repetitive behavior and/or restricted interests in early childhood. The prevalence is higher in male children than in female children. As a complex neurodevelopmental disorder, the phenotype and severity of autism are extremely heterogeneous with differences from one patient to another. Genetics has a key role in the etiology of autism. Environmental factors are also interacting with the genetic profile and cause abnormal changes in neuronal development, brain growth, and functional connectivity. The term of exome represents less than 1% of the human genome, but contains 85% of known disease-causing variants. Whole-exome sequencing (WES) is an application of the next generation sequencing technology to determine the variations of all coding regions, or exons of known genes. For this reason, WES has been extensively used for clinical studies in the recent years. WES has achieved great success in the past years for identifying Mendelian disease genes. This review evaluates the potential of current findings in ASD for application in next generation sequencing technology, particularly WES. WES and whole-genome sequencing (WGS) approaches may lead to the discovery of underlying genetic factors for ASD and may thereby identify novel therapeutic targets for this disorder.

MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders

Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism.

Etiopathogenesis of Sheehan’s Syndrome: Roles of Coagulation Factors and TNF-Alpha

Sheehans Syndrome (SS) is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A), Factor V (G1691A), MTHFR (C677T and A1298C), PAI-1 4G/5G, and TNF-α (−308  G > A) gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A), Factor V (G1691A), and MTHFR (C677T and A1298C) polymorphisms were identified by real-time PCR. PAI-1 4G/5G and TNF-α (−308  G > A) gene polymorphisms were detected with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-α gene polymorphisms should be researched in the etiopathogenesis of SS.

Genetic expressions of thrombophilic factors in patients with Sheehan’s syndrome

Abstract Purpose: The aim of this study was to evaluate the roles of factors associated with coagulation in the etiology and pathogenesis of Sheehan’s syndrome (SS) which is a frequent cause of hypopituitarism in underdeveloped and developing regions of the world. Methods: Mean prothrombin time (PT), activated partial thromboplastin time (APTT) and expression levels of genes, which included methylenetetrahydrofolate reductase (MTHFR), angiotensin I converting enzyme (ACE), coagulation factor V (FV), FVII, FVIII and FIX in 44 patients with SS were compared with 43 healthy subjects. Results: The mean expression level of the ACE gene was significantly lower, while that of the FV gene was significantly higher in the patients with SS. No significant difference was found between the patients with SS and the healthy subjects in the comparisons of the remaining gene expression values, as well as in the PT and APTT values. Conclusion: An increased expression of the FV gene may be a contributing factor for the development of SS in some patients. Further studies are required to clarify the roles of coagulation disorders in the development of SS.

A preliminary study of the genes related to aggression and insensitivity to pain in autism spectrum disorders

ABSTRACT Objective: Autism spectrum disorders (ASDs) is a heterogeneous neuropsychiatric disorder with widespread abnormalities of social interaction and communication, showing severely restricted interests and extreme repetitive behavior. The relationship between aggressive behavior, insensitivity to pain, and ASDs could not be explained completely. Therefore, we aimed to contribute to the etiology by examining the gene expressions of OPRL1, TACR1, and HTR1E in patients with ASDs. Methods: This study was held in the Genome and Stem Cell Research Center of Erciyes University. In this present study, the expressions of OPRL1, TACR1, and HTR1E genes were studied in 22 ASD patients and 14 healthy controls. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used for gene expression studies. Results: There was a statistically significant difference in terms of the expression of the three genes, which we examined between the ASD patient and control groups. Positive and strong correlations were obtained between the three gene expressions in the ASD group and this finding was found to be statistically significant. Conclusions: Considering all these findings, large-scale and new researches are needed for revealing the roles of genes and their pathways which are related to aggression and insensitivity to pain in ASDs. Our results will lead to new research studies in this field.

A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone

Background and aims Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothelial nitric oxide synthase gene polymorphisms on ureteral stone disease in patients who were admitted to the emergency department with severe pain due to renal colic are examined. Materials and methods The study groups were designed as controls and patients. The control group was formed from the healthy volunteers who applied to the blood center next to the emergency service. The patient group comprised patients who were diagnosed with ureteral stone disease with severe pain. All of the genetic studies were based on extracted peripheral blood samples using the necessary procedures from the Genome and Stem Cell Center at Erciyes University (GENKOK). The data were analyzed with SPSS (IBM, ver 20, United Sate). Results The study group comprised 62 females and 138 males, and the control group comprised 64 females and 136 males. All of the stones that caused renal colic were found to be localized in the ureters and the ureterovesical junction. The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. The GG genotype of the eNOS‐G894T polymorphism was found in 108 patients in the study group and in117 of the healthy individuals. There was no statistically significant difference between the two groups regarding these data. Conclusion Although this study is the first in the literature to examine the relationship between renal colic and endothelial nitric oxide synthase gene polymorphisms, our study demonstrated that no relation was found.

Toll-Like Receptors in the Progression of Autosomal Dominant Polycystic Kidney Disease: TLRs in Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of chronic kidney disease. The intriguing role of innate immune system and inflammation become a target for potential therapeutic approach to slow progression. When toll‐like receptors (TLRs) signaling and their receptors activate, they start a cascade of intracellular signaling that induces the production of the inflammatory cytokines and chemokines. Thus, we aim to investigate the association of TLRs between progression of ADPKD. Ninety ADPKD patients and ninety matched controls were enrolled this prospective study and were followed during 3 years. TLR‐2 and TLR‐4 gene polymorphisms and expressions were measured. Hypertension was diagnosed with ambulatory blood pressure monitoring. Rapid progression was defined as sustained decline in estimated glomerular filtration rate (eGFR) of more than 5 mL/min per 1.73 m2 per year. TLR‐4Asp299Gly polymorphisms were significantly different between patient and control group (P < 0.05). Also, TLR‐2 and TLR‐4 gene expressions were significantly different between the ADPKD patients and the control subjects (P < 0.05). The expression levels of both TLR‐2 and TLR‐4 were found to be higher in the rapid progression groups comparing the slow progression group (P < 0.05). TLR‐2 gene expression, hypertension and uric acid were found to be independent risk factors in identifying rapid progression in ADPKD patients. TLR‐2 and TLR‐4 gene expressions are associated with rapid progression in ADPKD patients. TLRs may play a role in the progression of ADPKD.