Clinical, biochemical, and genotypical characteristics in urea cycle mitochondrial transporter disorders.

BACKGROUND: This study aimed to evaluate clinical, biochemical, and genotypic findings of patients diagnosed with urea cycle mitochondrial transporter disorders. CASE SERIES: In this study, patients followed up with the diagnosis of urea cycle mitochondrial transporter disorders in the pediatric metabolism outpatient clinic of Diyarbakir Children's Hospital were retrospectively examined. Height, weight, head circumference, gender, age at diagnosis, follow-up period, consanguinity history between parents, and treatments of the patients included in the study were evaluated. Eight patients suffering from urea cycle mitochondrial transporter disorders were enrolled in the study. Five patients were found to have biallelic variants of the SLC25A15 gene. Two patients were found to have biallelic variants of the SLC25A13 gene. Two of our patients presented with gait disturbances and were diagnosed with HHH syndrome. One patient presented with liver failure and was diagnosed with HHH syndrome. The other three patients were identified by family screening. Citrin deficiency was detected in two patients with cholestasis and hepatomegaly in the infantile period. Ornithine levels increased in three of our patients with HHH syndrome during the first month of treatment despite a protein-restricted diet and adequate caloric intake. CONCLUSIONS: Increasing patients' caloric intake with HHH syndrome improves their ornithine levels. Our patients with citrin deficiency recovered clinically and biochemically before seven months.

Prevalence of HLA B27 in Patients Diagnosed with Ankylosing Spondylitis (AS) in Diyarbakir, Southeastern Region of Turkey.

AIM: The research to be conducted on human leukocyte antigen (HLA)-B27 in patients diagnosed with ankylosing spondylitis (AS) in Diyarbakir between 2019-2021 is to contribute to the understanding of the prevalence and effect of this genetic marker in the local population. As a researcher working on HLA-B27 and AS, our focus is to research the following. HLA-B27 Prevalence: To determine the prevalence of HLA-B27 in patients diagnosed with AS during the specified period in Diyarbakir. This information can provide insight into the genetic factors associated with the disease in the local population. Disease Severity: Investigate the relationship between HLA-B27 positivity and severity of AS symptoms. To examine factors such as disease progression, pain levels, functional impairment, and quality of life in HLA-B27 positive patients compared to HLA-B27 negative patients. By Genetic Associations: To enable the discovery of potential genetic relationships between HLA-B27 and other genetic markers known to be associated with AS. To investigate whether there are any specific genetic variants associated with HLA-B27 that contribute to disease susceptibility or severity. Researchers: We recommend considering the following approaches to generate knowledge on this topic globally: Literature Review: Conducting a comprehensive review of the available scientific literature on HLA-B27 and AS. It is to describe relevant studies conducted globally and summarize their findings to provide a broader understanding of the subject. Collaboration and Data Sharing: To encourage cooperation with researchers from other regions or countries doing similar studies on HLA-B27 and ASs. By sharing our data and collaborating on analysis, we can improve the global perspective and generalizability of your findings. International Conferences and Journals: Presenting our research findings at international conferences focusing on rheumatology, genetics or related fields. To disseminate our findings globally is to submit your research articles to reputable journals specializing in AS or genetic studies. Online Platforms: Using online platforms such as Researchgate.net, academia.edu or social media networks to share our research findings, connect with other researchers in the field and participate in discussions on a global scale. By using these fields, it is possible to contribute to the global knowledge and understanding of the relationship between HLA-B27 and AS. It is also to obtain insights from studies carried out in other regions. MATERIALS AND METHODS: 198 (104 male and 94 female) patients who applied to Dicle University Faculty of Medicine Physical Therapy and Rehabilitation Clinic with AS symptoms between 2019-2021 and were referred to Dicle University Medical Biology and Genetics Department for evaluation. HLA-B27 positivity was included in our study as a case group. As the control group, 50 people (25 males, 25 females) were selected among the unrelated people who applied to our laboratory to be a bone marrow donor. In both groups, DNA isolation was performed from peripheral blood using the salt precipitation method. Rotar Gene Q device was used for real-time PCR analysis. As a statistical method in analysis; The prevalences of the variables of interest were calculated. The lower and upper limits of 95% were determined as the confidence interval. According to the presence of HLA 27 positivity, the mean of ESR, CRP, and age variables were compared. Mann-Whitney U test was used due to the small number of subjects. Also, correlations between ESR and CRP were calculated. Spearman rho correlation statistics were used as a statistical method. Analyzed. RESULT: Radiological examinations and laboratory tests were performed on 198 patients with suspicion AS and 50 healthy control group of 248 subjects. The prevalence of those with a definite diagnosis of AS was calculated as statistical analysis recalculated 20.16 (95% CI: 0.76-0.9552). The prevalence of HLA-B27 in 50 patients diagnosed with AS as a result of radiological examinations and laboratory tests was calculated as 92%. CONCLUSION: Our study is the first study covering the province of Diyarbakir in the Southeastern Anatolia Region, which we think will contribute to the literature in the evaluation of HLA-B27 positivity in AS patients. The prevalence of HLA-B27 in our region is higher than the prevalence in Turkey.

COMPARISON OF C-PEPTIDE LEVELS IN MONOGENIC FORMS OF DIABETES WITH OTHER TYPES OF DIABETES: A SINGLE-CENTER STUDY.

Objective: This study aimed to evaluate the utility of C-peptide levels in the differentiation of monogenic forms of diabetes from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in clinical practice. Subjects and Methods: A total of 104 patients aged >16 who visited the Dicle University's Faculty of Medicine between April 2011 and December 2020 and were diagnosed with monogenic diabetes by genetic analysis or with T1DM and T2DM were randomly selected for retrospective evaluation. The C-peptide levels of these patients at the time of diagnosis of diabetes were compared. Results: Of the 104 patients, 24 (23%) were diagnosed with maturity-onset diabetes of the young (MODY), 40 (38.5%) with T1DM, and 40 (38.5%) with T2DM. Median C-peptide levels (ng/mL) (interquartile range) were 1.78 (1.24-2.88) in MODY group, 0.86 (0.34-1.22) in T1DM group, and 2.38 (1.58-4.27) in T2DM group. Conclusions: There was a difference in C-peptide levels between MODY and T1DM groups but not between MODY and T2DM groups. As per clinical evaluations, although C-peptide levels of patients with MODY are similar to those of patients with T2DM patients, the possibility of C-peptide levels being similar to those required for T1DM diagnosis should also be considered.

Seroprevalence of serum HBsAg positivity and hepatitis delta virus infection among blood donors in Southeastern Turkey.

AIMS: HBV and HDV infection is still a serious health problem in Southeastern Turkey. In this study, we aim to investigate the prevalence serum HBsAg along with HDV infection among volunteer blood donors. MATERIALS AND METHODS: This single centre and prospective study was performed in 6200 consecutive volunteer blood donors admitted to the Central Blood Bank of Dicle University Hospital. All adult blood donors included males and females were screened for HBsAg positivity. The positive serum samples for HBsAg were assessed for total anti-delta antibodies using the micro-ELISA method. Serum samples of anti-delta antibody positive cases were then examined for the presence of serum HDV RNA by real time, reverse transcription PCR method. RESULTS: Six thousand two hundred adult volunteer blood donors were enrolled to the study. Of all analyzed blood donors, 6004 (96.8%) were men and 196 (3.2%) were women. Serum HBsAg positivity was found in 3% (186/6200) of 6200 blood donors. The mean age and female/male ratio of HBsAg positive cases (n=186) were 32.85±10.04 years and 12/174, respectively. Serum anti-delta antibodies were detected in 6.98% (13/186) of HBsAg positive cases. The mean age of anti-delta antibody positive cases (n=13) was 44.5±13.61 years and female/male ratio was 1/12. Moreover, 2 cases, (15.39%, 2/13) that were positive for anti-delta antibody, had serum HDV RNA positivity. CONCLUSIONS: It would be appropriate for HBsAg positive volunteer blood donors to be assessed regarding concurrent HDV infection as well. The magnitude of the contribution and benefit that this screening would provide to our region, which is endemic for HDV infection, is the early diagnosis and management of this devastating disease. The real viremia in these cases can be best shown by using sensitive real time PCR method for the presence of serum HDV RNA.

The insertion/deletion polymorphism in the ACE gene and chronic obstructive pulmonary disease.

An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.

Angiotensin-converting enzyme gene insertion/deletion polymorphism with metabolic syndrome in Turkish patients.

BACKGROUND: The ACE gene has received substantial attention in recent years as candidate for a variety of diseases. The most common polymorphism in ACE gene is the Insertion/Deletion (I/D, rs4646994) polymorphism located on intron 16. AIM: We investigated the association between metabolic syndrome (MS) and the insertion (I) - deletion (D) polymorphisms in the angiotensin converting enzyme (ACE) gene in south-east of Turkey. SUBJECTS AND METHODS: One hundred and sixty subjects, with 101 cases of MS and 59 age- and gender-matched healthy controls were included in the study. RESULTS: The frequency of ACE I/D polymorphism was found to be 49.5% for DD, 36.6% for ID, and 13.9% for II in the MSstudy group and 44.1% for DD, 42.4% for ID and 13.5% for II in the control group. Allele frequencies were found to be 0.68% for D and 0.32% for I allele in the study group with MS and 0.65% for D, 0.35% for I allele in the control group. The I/D polymorphism of the ACE gene, DD, ID, and II genotypes occurred with similar frequencies in the study group with MS and the control group with no significant differences (p<0.05). On applying one-way analysis of variance to different ACE gene polymorphic groups in patients with MS were not significantly associated to ACE gene polymorphism and waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HDL, and LDL (p<0.05). CONCLUSIONS: Further studies of patients in larger numbers and of different ethnic backgrounds may be necessary to elucidate the association between the ACE I/D gene polymorphism and MS.

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B.

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey.

PURPOSE: In view of the genetic risks for the next generation, the importance of careful evaluation of karyotypes and AZF microdeletions in male infertility prior to assisted reproduction is evident. In the present study, it is aimed to investigate the frequency and types of both major chromosomal abnormalities by using standard cytogenetic methods and Y chromosome microdeletions of infertile males with azoospermia and oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in southeast Turkey. METHODS: A total of 80 infertile males (52 were azoospermic, 25 oligospermic and 3 asthenospermic) were studied for the cytogenetic evaluation and molecular AZF screening program prior to use of assisted reproduction techniques. A detailed history was taken for each man. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Polymerase chain reaction (PCR) amplification by using 15 Y-specific sequence-tagged sites of AZF region was performed to screen the microdeletions in the AZF region of Y chromosome. RESULTS: Of 80 cases, 71 had normal karyotype (46,XY). The total prevalence of chromosomal abnormalities was found to be 11.2% (9/80), including seven patients with Klinefelter syndromes and two patients with balanced autosomal rearrangements. All of the patients with Klinefelter Syndrome had azoospermia, but carriers with translocation had oligospermia. The deletions of Y chromosome were seen in one patient (1.3%) with features of normal karyotype and azoospermia. Microdeletions were seen in the AZFc and AZFd regions. Neither AZFa nor AZFb microdeletions were detected. CONCLUSIONS: The occurrence of chromosomal anomalies and Y chromosome microdeletions among infertile males strongly suggests the need for routine genetic testing and counseling prior to employment of assisted reproduction techniques.

The association of brain natriuretic peptide and insulin resistance in obesity-related hypertension.

Hypertension is frequently associated with obesity and natriuretic peptide levels are reported to decrease in obese subjects. Both the lower brain natriuretic peptide (BNP) concentration and insulin resistance are suggested to be associated with hypertension. However, their involvement in obesity-related hypertension has not been clearly defined. Forty-four obese women (21 normotensive and 23 hypertensive) and 25 healthy women matched for age were included in the study. Anthropometrical parameters were determined. Serum BNP, fasting insulin and glucose concentrations, and lipid parameters were evaluated. Insulin resistance was calculated using Homeostasis Model Assessment (HOMA) and Quantative Insulin Sensitivity Check Index (QUICKI) formulations. Within the obese groups, HOMA and QUICKI reflected the increased insulin resistance in hypertensive obese subjects with a significant correlation to blood pressure. The decrease in BNP in the obese groups was in favour of the hypertensive obese subjects (31.43+/-6.43; 26.36+/-4.29; and 17.51+/-3.08 pg/ml, respectively) with a fractional statistical significance between the hypertensive obese group and the controls (P=0.047). Only for the obese hypertensive group, fasting glucose, HOMA and QUICKI were significantly correlated with BNP. Moreover, fasting plasma glucose (R(2)=0.22, P=0.007) and fasting plasma insulin (R(2)=0.39, P=0.03) were independently correlated with BNP only for the obese hypertensive group. It can be concluded that the decrease in BNP concentrations in the obese hypertensive subjects seem to be well correlated with the insulin resistance.

CYP17 genetic polymorphism in patients with endometrial hyperplasia and cancer.

We investigated the association of CYP17 gene polymorphism with the risk of having endometrial cancer and a well-known precursor of it, endometrial hyperplasia. Group A (control group) consisted of 35 patients who had histologically proven normal endometrium. Group B and C consisted of 18 and 30 patients who had endometrial hyperplasia with and without atypia, respectively. Group D consisted of 57 patients who had endometrial cancer. Venous blood samples were collected from patients in groups, and polymerase chain reaction was performed to determine the CYP17 gene polymorphism. Significant increase of A1/A1 and a decrease of A1/A2 genotype frequencies have been determined in patients with endometrial cancer and with atypical endometrial hyperplasia. No significant differences were found between groups in the frequency of A2/A2 genotype. There was no significant difference between the groups in the meaning of allele distributions. CYP17 polymorphism had correlation with endometrial atypia and cancer. Related effects of different types of CYP17 gene variants on the progression of hyperplastic endometrial cells into carcinoma should be evaluated in further studies. Progress in this area would help us modulate preventive treatments used in those actual high-risk group patients.

Eleven novel mutations in the NF2 tumour suppressor gene.

Eleven novel mutations were identified in the NF2 tumour suppressor gene in a panel of British NF2 patients. Screening was performed using a combination of heteroduplex and single-strand conformation polymorphism analysis on polymerase chain reaction amplified material.