The role of the progesterone receptor PROGINS variant in the development of fibromyalgia syndrome and its psychological findings.

Fibromyalgia syndrome (FMS), a chronic pain disorder of unknown etiology, is more common in women. This suggests that biological sex is important. Therefore, we performed an analysis to determine whether the progesterone receptor (P GR) gene Alu insertion (named P ROGINS) variant is associated with an increased risk of FMS in the Turkish population. A total of 288 subjects, including 138 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria and 150 healthy subjects, were evaluated. Genotyping of the P GR P ROGINS variant was determined by polymerase chain reaction (P CR) analysis. The results of the analyses were evaluated for statistical significance. There were no subjects in the control group carrying the T2 allele. The P GR P ROGINS T1/T2 genotype was more prevalent in both all patients and female patients compared to all controls and female controls (p = 0.001, p = 0.003, respectively). A statistically significant relationship was observed in both all patients and female patients when compared to the control group according to T1/T1 vs. T1/T2+T2/T2 (p < 0.000, p < 0.001, respectively). The current study suggests that the P GR Alu insertion variant T2 allele might influence FMS susceptibility in the Turkish population. Large-sample sizes and studies of different ethnicities are required to further evaluate the association between this variant and FMS.

Vascular endothelial growth factor I/D variant and postmenopausal osteoporosis risk in the Turkish population.

INTRODUCTION: Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder manifested by low bone mineral density and increased fracture risks in postmenopausal women. Vascular endothelial growth factor (VEGF) has been shown to play an important role in bone formation. In this study, we investigated the potential association between the VEGF insertion/deletion (I/D) variant (rs35569394) and PMOP in a cohort of postmenopausal Turkish women. METHODS: This study included 300 women, including 150 PMOP patients and 150 healthy postmenopausal women. A T score was used in the diagnosis of OP. DNA was extracted from all subjects. The VEGF I/D polymorphism was analyzed by the PCR method. The Hardy-Weinberg equilibrium (HWE) test and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. RESULTS: The mean age of patients aged between 40 and 74 was 60.32 ± 8.65. The frequency of the I/I, I/D, and D/D genotypes was 7.34% versus 6.66%; 67.33% versus 65.34%; and 25.33% versus 28%, in patients and the control group, respectively. The allele frequencies were I: 41% (patients) and 39.4% (controls); D: 59% (patients) and 60.66% (controls). There was no statistically significant difference in the VEGF - 2549 I/D allele and genotype distribution between patients with PMOP and control subjects (p = 0.349, p = 0.864, respectively). CONCLUSION: Our results showed that the VEGF I/D variant was not a significant factor in the development of PMOP in a Turkish population sample. These findings need confirmation in other ethnic populations.

Evaluation of the association COMT Val158Met variant and childhood trauma on aggression in Turkish SCZ patients.

Childhood trauma is a serious form of stress that makes individuals more vulnerable to developing Schizophrenia (SCZ). Many studies have predicted the association between the catechol-O-methyltransferase (COMT) gene Val158Met variant and aggressive attack. We aimed to investigate the association the COMT variant and childhood trauma on aggression in Turkish SCZ patientsThis study included 89 patients diagnosed with SCZ. Childhood Trauma Questionnaire (CTS) and Overt Aggression Scale (OAS) were used to assess childhood trauma and aggression. COMT Val158Met variant was analyzed by PCR-RFLP method from isolated DNAs.There was no statistically significant difference in comparing the COMT genotype distribution and clinical characteristics including suicide attempts, self-destructive behavior, crime history, substance, alcohol and tobacco use. When we evaluate Spearman's rank correlation coefficients between CTQ and OAS, the correlation between the OAS and CTQ scores of the patients was statistically significant except for the sexual abuse subgroup of the CTQ. In the univariate logistic regression analysis, in which the dichotomized OAS score was accepted as the dependent variable, it was found that age, suicide attempt, substance abuse, and CTQ total score significantly predicted the higher OAS scores. In the multivariate logistic regression analysis, which included the variables that predicted OAS significantly, age, suicide attempt, and total CTQ score were determined as independent variables predicting OAS.Because of the phenotypic complexity in SCZ, it is difficult to draw strong conclusions about COMT and to highlight a definitive relationship. Larger-scale studies are needed to examine the multifactorial inheritance pattern of schizophrenia in different dimensions.

Evaluation of the 18-bp deletion/insertion variant of the VEGF gene in athletes.

The skeletal muscle capillary supply mainly determines the highest exercise capacity. Vascular endothelial growth factor (VEGF) is the major growth factor during the angiogenesis process. Therefore, we aimed to investigate whether the VEGF insertion/deletion (I/D) variant differs between athletes and sedentary controls in the Turkish population. Three hundred sixteen subjects, including 146 athletes from different branches and 170 sedentary people, voluntarily participated in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analysis for the VEGF I/D variant. The results were evaluated statistically. In this study, the athletes and the controls showed a statistically significant difference in the genotype and allele distribution of the VEGF I/D variant. The athletes had a more prevalent D allele and D/D genotype than the controls (p = 0.008 and p = 0.034, respectively). There was a statistically significant association between the patients and the controls in terms of D/D vs. I/I + I/D genotypes (p = 0.018). There was no significant difference in VEGF I/D genotype distribution according to sports branches. Athletic performance is a complex trait influenced by genetic and environmental factors. As far as we know, this is the first study to evaluate the VEGF I/D variant in athletes in Turkey. According to our results in this study, we concluded that the VEGF I/D variant, D/D genotype, and D allele are associated with sport performance in the Turkish population. However, there is a need for studies with large samples in which environmental and emotional factors will also be taken into account.

IL2RA rs2104286 and IL2 rs2069762 polymorphisms may be associated with bipolar disorder and its clinical findings.

Study results supported that immuno-inflammatory pathways in the brain and environment contribute to the etiopathogenesis of bipolar disorder (BD), a chronic affective disease. Our study aimed to assess the relationship between BD risk and interleukin 2 (IL2) and interleukin 2 receptor subunit alpha (IL2RA) variants in a Turkish population. Genomic DNA from 86 diagnosed BD patients and 100 healthy blood donors was extracted. IL2RA rs2104286, IL2 rs2069762, and IL2 rs2069763 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. It was compared to the relationship between the genotype distributions of these variants and clinical characteristics. Results were evaluated statistically. A statistically significant difference in the genotype distribution of the IL2RA rs2104286 variant was found between patients and controls. There was no GG genotype in the patient group. The IL2RA rs2104286 AA genotype was more common in the patient group than the controls, and the AG genotype was higher in the controls compared to the patients (p = 0.001, p = 0.001, respectively). The IL2 rs2069762 and IL2 rs2069763 genotype distributions did not differ between the patient and control groups (p > 0.05). We found that the clinical global impression severity (CGI-S) score was higher in those with IL2 rs2069762 TG and GG genotypes. In this study, we showed for the first time that the genotype distribution of IL2RA rs2104286 and IL2 rs2069762 is associated with BD susceptibility and CGI-S score in a Turkish population.

Evaluating interleukin-6 levels and the rs1800795 variant in Turkish patients with COVID-19: a prospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a multisystem disease of global significance. Interleukin (IL)-6 is a soluble cytokine with a pleiotropic effect on inflammation and the immune response. OBJECTIVES: Investigate the relationship between the interleukin 6 (IL6) rs1800795 variant and IL6 level in Turkish patients with COVID-19 disease. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Real-time polymerase chain reaction (RT-PCR)-positive and/or chest computerized tomography (CT) scan-compatible COVID-19 patients were enrolled in the study. The clinical data and whole blood samples were collected from April 1, 2020, to August 1, 2020. IL6 rs1800795 genotyping was performed by the PCR-restriction fragment-length polymorphism (RFLP) method in 148 patients. Serum IL-6 concentrations were measured using the ELISA method in 89 patients. We evaluated the patients in three groups: asymptomatic, symptomatic, and intensive care unit patients. MAIN OUTCOME MEASURES: IL6 rs1800795 genotype frequencies and serum IL-6 levels in COVID-19 patients with different clinical presentations. SAMPLE SIZE: 148 cases. RESULTS: IL6 rs1800795 GG genotype and G allele frequency increased in PCR positive patients compared to PCR-negative patients (p ˂ 0.000). IL6 rs1800795 GC genotype and C allele frequency were lower in PCR-positive patients than in PCR-negative patients. IL6 rs1800795 GG genotype and G allele frequency were higher in asymptomatic patients than in the symptomatic and intensive care unit groups. The IL6 rs1800795 C allele frequency was lower in asymptomatic patients than in the symptomatic and intensive care unit groups. IL6 rs1800795 GG genotype and G allele frequency were higher in CT negative patients than CT positive patients, while IL6 GC genotype and C allele frequency were higher in CT positive patients than negative patients. IL6 level elevation was seen in the asymptomatic patients compared to the symptomatic and intensive care unit groups. CONCLUSIONS: These findings suggest that IL6 rs1800795 may contribute to the susceptibility of COVID-19 in people to Turkish origin. LIMITATIONS: Further large-scale studies in different genetic populations are needed as this is a single-center, prospective study.

MEFV gene pathogenic variants: a risk factor for dysmenorrhea in the Turkish population.

BACKGROUND/AIM: The Mediterranean fever (MEFV) gene codes for protein pyrin, which is among the modulators of inflammasome activity in innate immune cells. It was suggested that there is a relation between MEFV variations and inflammatory diseases. The aim of this study was to investigate MEFV gene variations in the patients with primary dysmenorrhea. METHODS: The prevalence of common MEFV gene variations (M694V, M680I, V726A, E148Q and R202Q) was investigated in 145 young women with primary dysmenorrhea and 135 unrelated healthy controls. MEFV gene variations were genotyped using PCR-based RFLP assay. RESULTS: Number of childbirth and marriage were significantly lower in the study group than the controls, respectvely (p < 0.001, p = 0.001). Family history was statistically higher in the patient group (p < 0.001). In total, MEFV genotype and allele frequencies were significantly higher in patients than controls, respectively (p = 0.008 and p = 0.005, respectively). It was found that MEFV gene E148Q allele was more common in patient group (p = 0.039). MEFV R202Q A allele was higher in the patients than the controls (p = 0.045). A significant association was observed when the patients were compared with the controls according to R202Q variant AA versus GG+GA genotypes (p=0.020). CONCLUSION: Our findings suggest that MEFV variations may be a risk factor for patients with dysmenorrhea in a Turkish cohort.HighlightsThere are very few studies in the literature regarding the relationship between pathological variants of MEFV and dysmenorrhea disease.The common MEFV mutations/variants were evaluated in primary dysmenorrhea patients.Family history was statistically higher in the patient group (p <.001).MEFV gene variations were found 52 (35.9%) in patients and 29 (21.5%2) in controls.MEFV gene allele frequency was significantly higher in-patient group than control (p =.005).

Association of MIF-173G/C, IL-4 VNTR, and IL-1RA VNTR variants with FMF-related amyloidosis in a Turkish cohort.

The most important complication of familial Mediterranean fever (FMF) is secondary amyloidosis. The aim of this study is to investigate the risk of developing FMF-related amyloidosis with macrophage migration inhibitory factor (MIF), interleukin 4 (IL-4), and IL-1 receptor antagonist (IL-1RA) variants. This study included 62 FMF patients with amyloidosis, 110 FMF patients without amyloidosis, and 120 controls. The clinical information of the patient groups was compared. MIF-173G/C, IL-4 variant number tandem repeat (VNTR), and IL-1RA VNTR variants were analyzed for all participants. The use of colchicine, pleurisy, and appendectomy was more common in FMF patients with amyloidosis than in FMF patients without amyloidosis. MIF-173G/C C/C genotype and C allele were higher in both patient groups compared to controls. IL-1RA VNTR A1/A2 and A1/A4 genotypes and A1-A4 alleles were more common in both patient groups than controls. The IL-4 VNTR P1 allele was more common in FMF patients with amyloidosis compared to controls. The MIF-173G/C allele and the IL-1RA VNTR A1-A4 allele are associated with FMF in the Turkish population but not with amyloidosis risk in FMF patients. The IL-4 VNTR P1 allele is more common in FMF patients with amyloidosis than in healthy individuals.

The evaluation of superoxide dismutase 1 gene insertion/deletion variant in athletes.

OBJECTIVE: Regular exercise benefits health by increasing the body's antioxidant defenses. However, excessive exercise can produce excessive reactive oxygen species, which can lead to oxidative stress. Superoxide dismutase is the primary enzyme involved in the elimination of reactive oxygen species. This study aimed to determine the relationship between the SOD1 gene insertion/deletion variant and elite athletes. METHODS: A total of 305 subjects, including 165 elite athletes from different branches and 140 sedentary individuals, participated in this study. The SOD1 insertion/deletion variant was genotyped using polymerase chain reaction. The results were evaluated statistically. RESULTS: There was no statistical significance between the athletes and control groups in terms of SOD1 insertion/deletion genotype distribution and allele frequency. Then, we evaluated the groups as females and males. There were no female athletes carrying the D/D genotype. The SOD1 I/I genotype and the I allele were more prevalent in female athletes than in the control group. There was a significant difference in terms of SOD1 I/I: I/D+D/D in females (p=0.028). SOD1 genotype and allele distribution did not differ between male athletes and male controls. CONCLUSION: As far as we know, this is the first study to evaluate the SOD1 insertion/deletion variant in athletes in Turkey. Our results showed that the SOD1 I allele was more common in female athletes, but not in male athletes.

Lack of association between VNTR variant of the circadian gene (PER3) and major depressive disorder in a sample of a Turkish population.

Major depressive disorder (MDD), which is a prevalent psychiatric disorder, is characterized by sleep-wake disturbances. An underlying circadian rhythm disorder mainly may cause these disturbances. The study presented here was designed to investigate the existence of Period Circadian Regulator 3 (PER3) gene VNTR variant in MDD patients in Turkish population. A sample of 118 patients with MDD and 150 healthy volunteers were included in the study. The PER3 VNTR genotyping was performed on DNA by polymerase chain reaction (PCR) using specific primers. The prevalence rates of genotypes of 5/5, 5/4, and 4/4 profiles for the PER3 variant were 30.5%, 55.9%, and 13.6%, respectively, in patients with MDD, and 23.3%, 57.3%, and 19.3%, respectively in the control group. No significant difference was observed between the two groups in terms of either genotype distributions or allele frequencies of the VNTR variant of the PER3 gene (p > 0.05). There was no statistically significant association between the patients and the controls in terms of 5/5 + 4/5 versus 4/4 and 5/5 versus 4/5 + 4/4 (p > 0.05). The present results suggest that the PER3 VNTR variant was not associated with MDD in the Turkish population. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of this variant in MDD.

Association of ACE ID, MTHFR C677T, and MIF-173GC variants with the clinical course of COVID-19 patients.

The course of coronavirus disease-2019 (COVID-19) differs from person to person. The relationship between the genetic variations of the host and the course of COVID-19 has been a matter of interest. In this study, we investigated whether Angiotensin-Converting Enzyme (ACE) ID, Methylenetetrahydrofolate Reductase (MTHFR) C677T, and Macrophage Migration Inhibitory Factor (MIF)-173GC variants are risk factors for the clinical course of COVID-19 disease in Turkish patients. One hundred COVID-19 patients were included in the study. The diagnosis of COVID-19 was made using Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Chest Computed Tomography (CT). The patients were evaluated in 3 groups: intensive care, service, and outpatient treatment. ACE ID, MTHFR C677T, and MIF-173GC variants were genotyped by PCR-Restriction Fragment Length Polymorphism (RFLP) methods. When the genotype distribution between the groups was examined, it was found that the frequency of the ACE DD genotype and the D allele was higher in the intensive care group compared to the hospitalized and outpatient groups. MTHFR C677T CT genotype T allele and MIF-173GC, CC genotype C allele were more prevalent in the intensive care group compared to other groups. Patients with PCR-positive results had a higher MTHFR C677T C/C genotype and C allele. In CT-positive patients, the MTHFR C677T CT genotype and the MIF-173GC, G allele were more common. It is predicted that genetic predisposition may contribute to COVID-19 morbidity and mortality. Our results show that ACE ID, MTHFR C677T, and MIF-173GC variants affect the course of COVID-19 disease in the Turkish population.

The effect of a 18 bp deletion/insertion variant of VEGF gene on the FMF development.

Objective: Familial Mediterranean fever (FMF) is one of the most common inherited autoinflammatory diseases. Angiogenesis is a feature of inflammatory activation and part of pathogenic processes in autoimmune diseases. Therefore, this study aimed to investigate the role of the Vascular endothelial growth factor (VEGF) gene insertion/deletion (I/D) functional variant in FMF Turkish patients. Methods: MEFV gene mutations were detected in all patients. The FMF patients (N:105) and the healthy controls (N:100) were genotyped for the VEGF I/D variant using PCR followed by agarose gel electrophoresis. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ2-tests. Results: The mean age of patients was 25.46 ± 10.09. Fifty-nine patients (56.2%) had two or more MEFV gene mutations. The most common MEFV mutation was M694V/M694V. The VEGF I/D variant genotype distribution exhibited a statistically significant difference between the patients and the controls. VEGF I/D genotype was higher in controls compared to patients, while D/D genotype was higher in patients compared to the controls (p = 0.003, p = 0.013, respectively). When we examined the clinical findings, joint pain was more common in patients with VEGF D/D and I/D genotypes compared to I/I genotype (p = 0.043). Although not statistically significant, the most common genotype in patients with two or more MEFV mutations was VEGF D/D (28.6%). Conclusion: The results provided evidence supporting that the D/D genotype of the VEGF I/D variant is associated with an increased risk of FMF in a group of Turkish populations.

Role of VEGF I/D variant in suspectibility to odontogenic cyst formation.

Odontogenic cysts, are located in the jawbones, filled with fluid surrounded by epithelial lining and fibrous connective tissue. Vascular endothelial growth factor (VEGF) can induce physiological and pathological angiogenesis and is an endothelial cell-specific mitogen. The aim of the present study was to investigate whether any possible association between the VEGF insertion/deletion (I/D) variant and odontogenic cyst in Turkish population. Clinical information and venous blood samples were collected from 62 odontogenic cyst patients and 98 healthy controls. DNA was isolated from peripheral blood leukocytes. Genotyping of the VEGF I/D variant was done by the polymerase chain reaction (PCR) method. There was a statistically differece in terms of VEGF I/D allele frequencies between patients and controls. VEGF I/D variant I allele frequency was more prevalant in patients compared to controls (p = 0.006411, OR: 2.08, 95%Cl: 1.322-3.272). A statistically significant association was observed when the patients were compared with the controls according to D/D + I/D versus I/I genotype (p = 0.0508, OR: 1.925, 95%Cl: 0.872-4.246). The genotype distribution of VEGF I/D was not statistically different between patients and controls (p > 0.05). For the first time, our results provided evidence supporting the odontogenic cyst formation associated with the I/D variant at the promoter region of the VEGF gene in a group of Turkish population. Although it was seen in our study that the I/D variant in the promoter region of the VEGF gene supports odontogenic cyst formation, large-scale studies are needed to elucidate the effect of this variant on odontogenic cysts.

Effect of IL-6 -174G/C and -572G/C variants on susceptibility to osteoarthritis in Turkish population.

Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage in which inflammatory mechanisms play a major role in the pathogenesis. Interleukin-6 (IL6), a multifunctional cytokine, can trigger osteoclast differentiation and bone resorption. Our purpose in this study was to evaluate the association of IL-6 -174 G/C (rs1800795) and -572 G/C (rs1800796) variants with the susceptibility to OA. One hundred fifty OA patients and 150 healthy individuals were enrolled in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene variants. The results of analyses were evaluated for statistical significance. The pain intensity was assessed using the Visual Analogue Scale (VAS). There was a statistically significant difference in the genotype and allele frequencies of the IL-6 -174 G/C variant between patients with OA and control groups (p = 0.001, p = 0.002, respectively). IL-6 -174 G/C GG genotype and G allele were more prevalent in patients with OA. We found that the IL-6 -572 G/C variant was not different between patients and controls in either genotype distribution and allele frequency. IL-6 174 G/C and -572 G/C loci GG-GG combined genotype was significantly higher in OA patients (p = 0.00). Our study suggests that there was a strong association between the IL-6 -174 G/C variant and OA in the Turkish population. Further studies on populations of different ethnic background are necessary to prove the association of IL-6 variants with OA.

VEGF and eNOS variants may influence intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) is a common and complex condition. Vascular endothelial growth factor (VEGF) is one of the key regulators of angiogenesis and vascular permeability. Nitric oxide (NO) plays a role in various physiological events. The endothelial nitric oxide synthase (eNOS) that catalyses NO generation are crucial for the regulation of NO level. This study aimed to evaluate the association between VEGF/ eNOS gene variants with IDD. MATERIALS AND METHODS: Two hundred ninety-one subjects (111 IDD patients and 180 controls) were included in the present case-control study. VEGF -2549 insertion/deletion (I/D) and eNOS VNTR variants were analysed by PCR method. The results of this analysis were evaluated for statistical significance. RESULTS: There were no statistically significant differences in genotype and allele distribution of VEGF -2549 I/D/ eNOS VNTR variants between IDD patients and control subjects. We then evaluated the association between the allele frequencies of these variants and clinical features of IDD. Lumber IDD was more common in patients carrying VEGF I/D variant D allele (p < 0.001). Also, patients with lumbar disc herniation, cervical disc herniation, lumbar stenosis, and lumbar IDD had more 4 b allele (p = 0.005, p < 0.001, p < 0.001, and p = 0.03, respectively). CONCLUSIONS: In conclusion, this study demonstrates first time that some clinical characteristics of IDD have been associated with allele frequencies of VEGF -2549 I/D/ eNOS VNTR variants.

Genotype Distribution and Prevalence of High-Risk Human Papillomavirus Infection among Women in Samsun Province of Turkey.

BACKGROUND: The human papillomavirus (HPV) is an important public health problem that can cause cervical cancer. HPVs were classified into high-risk (HR-HPV) and low-risk (LR-HPV) types. In this study, we aimed to determine the prevalence and genotype distribution of HR-HPV infection in Samsun province in Turkey. METHODS: Cervical smear samples taken from 5406 women over a 23-month period were evaluated for the presence of HPV infection. The detection of HPV genotypes was performed using RT-PCR technology. HPV detection and genotyping were performed using RT-PCR method. HR- HPV types are divided into 3 groups as type 16,  type 18 and other types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, with or without type 16 and 18).  The results were evaluated statistically. RESULTS: The mean age of HR-HPV positive patients was 39.56 years (20-68 years). The prevalance of HR-HPV types did not differ between different age groups (p˃0.05). Overall, 9.17% of women (496/5406 samples) were found to be positive at least one type of HR-HPV. HPV type 16 was detected in 28.62%, type 18 in 9.67%, and other types in 78.83%. The most common HR-HPV type was other types (p˂0.001). Type 16 was most common than type 18 (p˂0.001). The patients were evaluated by dividing them into 6 age groups. Type 16 positivity was higher in 30-39 ages while type18 and other types positivity were higher in the 40-49 age group. When the 23-month period of HPV test was evaluated according to months and seasons, the highest prevalance was seen in June 2021 and Summer 2021. CONCLUSION: To our knowledge, this is the first large-scale study of HR-HPV prevalence and genotype distribution among women in Samsun Province of Turkey.  The other types containing one or more types made up the majority of the studied population.

ACTN3 R577X variant: could it be a determinant of sports performance in elite athletes in a Turkish population?

ACTN3 gene, which encodes a-actinin-3 and actin-binding protein, has been found to be associated with strong athletic performance, especially among track and field athletes. Therefore, in this study, our aim was to compare the allelic and genotype frequencies of the ACTN3 R577X variant among elite athletes specialized in different branches, and nonathletic controls in Turkey. In the present study, 316 subjects, including 168 athletes and 148 sedentary controls were genotyped for the ACTN3 R577X variant. Genotyping was conducted by polymerase chain reaction (PCR) method. Additionally, we evaluated the groups by dividing them as females and males. There were 48 females and 120 males in the athletes group, and 43 females and 105 males in the control group. Genetic associations were evaluated by chi-squire test or Fisher's exact test. There was a significant difference between the athletes and controls in terms of the ACTN3 R577X variant. ACTN3 RR and XX genotypes increased in the controls compared to the athletes, while RX genotype was higher in the athletes than the controls (P = 0.030). Then we evaluated the groups by separating them as females and males. Genotype distribution of the ACTN3 R577X differed between the male athletes and the male controls (P = 0.046). ACTN3 R577X RX genotype increased in the male athletes compared to the male control (P = 0.046). But ACTN3 R577X genotype and allele distribution was not significant between female athletes and female control group (P>0.05). As far as we know, this study is the largest series examining the ACTN3 R577X variant in Turkish athletes. Our results support that the ACTN3 R577X variant has a heterozygous advantage in athletic performance in the Turkish population. However, epigenetic, gene-gene and gene-environment interactions affects athlete performance should not be forgotten.

A circadian rhythm gene (PER3) VNTR variant as possible risk factor in cohort of Turkish females with primary dysmenorrhea.

Primary dysmenorrhea (PDM), which is the most prevalent problem related to the menstrual cycle in women of reproductive age, is due to sleep disorders and negative moods. Circadian rhythms, which are the immediate 24-h processes, enable an organism to adapt the suitable physiological responses to the environmental light-dark changes. Disturbed circadian rhythms are closely associated with several diseases, including sleep disorders. It has been reported that variable number tandem repeat (VNTR) variant in the coding region of circadian rhythm gene PERIOD 3 (PER3) affects sleep. Therefore, in the present study, we investigated the association between PDM and PER3 VNTR variant in Turkish females. A sample of 122 females with PDM and 150 healthy females were included in the study. Genoytyping of PER3 VNTR variant was performed on DNA by polymerase chain reaction (PCR) analysis using specific primers. We evaluated the relation between PER3 VNTR variant and PDM by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). In our analyses of genotype data collected from total 272 subjects, we found that the PER3 VNTR variant was associated with development of PDM [codominant model (5/5 vs. 4/4 + 4/5): OR = 0.664; 95% CI, 0.39-1.10; p = 0.05). The three genotypes of the VNTR variant (4/4, 4/5, and 5/5) and their allelic frequencies showed nonsignificant differences between patients and control group (p > 0.05). In summary, PER3 VNTR variant may be associated with PDM in a Turkish female. However, further studies in different ethnic populations are needed to address the full role of this variant in PDM.

What are the roles of global DNA and APC 2 gene promotor hypermethylation in multiple myeloma?

BACKGROUND: In today's practice, gene-based approaches come to the fore in the determination of prognosis and treatment preferences of multiple myeloma (MM). DNA methylation is one of the new approach parameters. DNA methylation occurs by the addition of a methyl group to cytosines in CpG dinucleotides. In this study, besides comparing the global DNA and APC 2 gene promotor hypermethylation between our patients with MM and healthy control group, we aimed to demonstrate the effect of hypermethylation on MM treatment responses and survival. METHODS AND RESULTS: 38 patients diagnosed with MM between January 2016 and January 2020 and 50 healthy controls were included in the study. The initial hypermethylation of the patients and the healthy control group were statistically analyzed. In addition, the increase in hypermethylation in the MM group before and after the first series of treatments were analyzed within themselves. There is a significant difference between the patients with MM diagnosis and the healthy control group in terms of the initial global hypermethylation (P = 0.001). In patients with MM, hypermethylation was significantly higher. Global hypermethylation in the post-treatment measurements was significantly increased in comparison to the pre-treatment state (P = 0.012). In terms of APC 2 promotor gene-specific hypermethylation, no significant differences were detected between pre- and post-treatment values (P = 0.368). CONCLUSIONS: This study represents valuable data with the initial global DNA hypermethylation results in the MM patient group and the increase in hypermethylation post-treatment. it will shed light on future studies.

Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience.

BACKGROUND: Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients. METHODS: Medical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism. RESULTS: eNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype (p = 0.035, 0.023). CONCLUSIONS: eNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.