Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

Objective: To investigate the expression levels of genes (SLC6A3, SLC6A4, SLC1A2, SLC18A2, MAOA, COMT, GLYAT, GRM5, DRD4, TPH1, and ADRA2C) associated with attention deficit hyperactivity disorder (ADHD) by pre and post-treatment with methylphenidate to see if they may serve as biomarkers in the etiopathogenesis of diseases. Materials and Methods : Thirty-five ADHD-diagnosed children and 38 healthy controls were included and divided three groups as control, pre-treatment and post-treatment group. After the isolation of mRNA from peripheral blood samples of participants, qPCR was performed using cDNA obtained from mRNA via reverse transcription method. Result: Elevated SLC6A3 and decreased SLC6A4, SLC1A2, SLC18A2, ADRA2C, MAOA, COMT, GLYAT, DRD4 and TPH1 genes' expression levels of childiren with ADHD were detected (p

Iron metabolism has long been linked to metabolic syndrome (MetS), but it is still unclear at which step—iron sensing, hepcidin regulation, export, transport, or storage—genetic variation matters the most. There are almost no studies on iron metabolism genes in Kazakhs in particular. Using whole-exome sequencing (WES) data from 96 Kazakh adults (52 with MetS), we examined 18 SNPs across six iron metabolism genes—HFE, SLC40A1, TMPRSS6, FTL, TFR2, and TF. Associations with iron biomarkers and MS components were tested by linear regression adjusted for age, sex, and BMI, with FDR correction, haplotype analysis, and bootstrap mediation analysis. Significant effects clustered at two distinct steps of iron metabolism: hepcidin regulation (TMPRSS6) and iron transport (TF). The T allele of TF rs12769 raised serum transferrin (β = +0.32 g/L; p_FDR = 0.002) while lowering both TSAT (β = −4.25%) and ferritin (β = −0.36 log-units); haplotype analysis confirmed rs12769 as the driver. The TMPRSS6 C–G–C haplotype was associated with lower fasting glucose (β = −1.19 mmol/L; p = 0.023), and TF rs12769 emerged as a robust FDR-significant determinant of serum transferrin (p_FDR = 0.002). Bootstrap mediation analysis (5000 iterations) showed that the TMPRSS6 effect on glucose is not mediated by ferritin, serum iron, transferrin, TSAT, or sTfR (all ACME p > 0.20), while Total and Direct Effects remained robust (p ≤ 0.054). In Kazakhs, iron-metabolism genes appear to influence fasting glucose through direct mechanisms not captured by the standard iron biomarker panel; alternative pathways involving hepatic enzymes, hepcidin, or inflammation warrant investigation in larger cohorts.

Background: In this study, we aimed to analyze androgen receptor (AR) gene mutations in five members of a family with complete androgen insensitivity syndrome (CAIS). Methods: Peripheral blood samples were collected from the proband and four relatives (mother, sister, and two aunts). Cytogenetic imaging and chromosomal analysis were per-formed to elucidate the genetic basis of the condition. Clinical Exome Sequencing (CES) was conducted to identify candidate variants, which were subsequently validated using Sanger sequencing. Evolutionary conservation analysis was performed for the identified AR gene mutation. Results: Our analyses revealed that the proband, sister, Aunt I, and Aunt II exhibited a 46,XY karyotype and carried the SRY gene. The mother, however, had a 46,XX karyotype, and did not carry the SRY gene, confirming X-linked recessive inheritance of the condition. CES results demonstrated that the proband, sister, Aunt I, and Aunt II harbored a hemizygous c.2246C>T (p.Ala749Val) mutation, while the mother carried this mutation in a heterozygous state. The presence of this mutation was confirmed by Sanger sequencing. Evolutionary conservation analysis indicated that the mutation is conserved among vertebrates. Conclusion: in conclusion, we identified a novel missense mutation (c.2246C>T) in the AR gene in five members of a CAIS-affected family, which has not been previously reported in the literature.

Background Essential tremor (ET) is the most common movement disorder. Propranolol is a first-line medication for ET. We aimed to evaluate the effect of propranolol on the expression of poly (ADP-ribose) polymerase 1 (PARP1) and DNA polymerase beta (POLB) genes, which are known to be related to neurodegenerative diseases, in patients with ET. Methods Thirty-five healthy volunteers and thirty-five patients followed up with essential tremors were included in a non-randomized control experimental study. Expressions of PARP1 and POLB genes were compared between the control group and the patient group. In addition, pre- and post-treatment gene expression levels and Fahn-Tolosa-Marin tremor scale values of the patient group were compared after 8 weeks of propranolol treatment. The Wilcoxon rank and Mann Whitney U tests were used to analyze the data. Results At baseline, PARP1 expression was significantly lower in the ET group than in the control group. (p<0.001). POLB gene expression was significantly higher in the pre-treatment ET group than in the controls (p<0.05). There was no significant difference in PARP1 expression levels before and after 8 weeks of propranolol treatment. POLB gene expression was significantly higher in the pre-treatment group than in the post-treatment group (p<0.001). Conclusion Propranolol significantly decreased POLB gene expression but there was no significant difference in PARP1 gene expression levels in the patient group, after 8 weeks of propranolol treatment.

Background: Metabolic syndrome (MetS), a cluster of cardiometabolic abnormalities including elevated blood pressure, impaired glucose regulation, dyslipidemia, and increased waist circumference is increasingly recognized as a condition linked to both physical and psychological health risks. This study aims to investigate genotype-specific differences in psychological distress between healthy individuals and those with metabolic disorders, as well as to examine potential gene metabolic status interactions. Methods: This study is a cross-sectional analysis conducted in Turkistan city in the Southern region of Kazakhstan. Participants (healthy and those with metabolic syndrome) were invited to take part in the study by random sampling from the Khoja Akhmet Yassawi Kazakh-Turkish International University Medical Center. Consenting individuals provided a genetic analysis. Psychosomatic indicators were assessed using the Perceived Stress Questionnaire (PSQ) and the Depression, Anxiety, and Stress Scale (DASS-21). Results: A total of 200 individuals participated, with an approximately 3:1 ratio of women to men. The mean age in years was 50.4 ± 9.5 and 48.8 ± 7.7 for men and women, respectively. Preliminary analyses showed variations in cognitive and psychosomatic measures among individuals with metabolic syndrome, but no associations with genetic variants, and no significant group differences across key psychosomatic indicators when stratified by metabolic or genetic factors. However, a significant difference in LPL-Anxiety between genotypes GA-GG (p < 0.05) was found. Conclusions: Variations in metabolic and genetic factors within the studied population were not associated with measurable differences in stress or depressive symptoms.