Estrogen Receptor 1 Gene rs22346939 and rs9340799 Variants are Associated with Major Depressive Disorder and its Clinical Features.

OBJECTIVE: Major Depressive Disorder (MDD) is a major health problem worldwide. Estrogen interacts with the central nervous system and has been shown to affect anxiety and depressive behavior. Estrogen mediates its effects by connecting its receptors, estrogen receptors 1 and 2. The purpose of this case-control study was to clarify the association between MDD risk and estrogen receptor 1 (ESR1) gene variants. METHODS: This study included 245 individuals (125 MDD patients and 120 healthy controls). Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technics were used for genotypingESR1XbaII (rs9340799) and PvuII (rs22346939) variants. RESULTS: There were statistically significant differences between the groups in terms of genotype frequencies of the ESR1PvuII (-397 T > C) variant (p = 0.049) but not for the XbaII (-351 A > G) variant (p > 0.05). However, a correlation was observed between MDD and ESR1XbaII variant after male participants were excluded (p = 0.028). Also, the high pain score of MDD patients was associated with the ESR1PvuII variant, especially in female patients (p = 0.021). According to the results of combined genotype analysis, AA-TC combined genotype was correlated with a decreased risk in patients with MDD compared to controls (p = 0.016), while the combined genotype of GGCC was associated with increased risk in the patients with MDD compared to controls (p = 0.042). CONCLUSION: The two ESR1 variants were associated with MDD risk and its features in both individual and combined forms.

Influence of ESR1 Variants on Clinical Characteristics and Fibromyalgia Syndrome in Turkish Women.

BACKGROUND: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain. It is more common in women than in men, and sex hormones may play a role in this predominance. Therefore, this research investigated the clinical findings among Turkish females and whether Estrogen-α (ESR1) gene variants are associated with FMS. METHODS: A total of 219 individuals were enrolled in this study. ESR1 variants (PvuII/XbaI) were genotyped using PCR-RFLP methods. The results of the analyses were evaluated for statistical significance. RESULTS: There was a significant association between the ESR1 PvuII and FMS risk among Turkish women. The ESR1 PvuII CC genotype and C allele were higher in the patients than those in the controls (p=0.021, p=0.007, respectively). A more statistically significant association was observed between the patients and the controls in terms of TT genotype vs. TC+CC genotypes (p=0.022). Also, there was a statistically significant association between the patients and the controls in terms of TT+TC genotype vs. CC genotypes (p =0.028). There was no significant association between patients and the control group concerning the genotype distribution and allele frequencies of ESR1 XbaI (p>0.05). Headache was seen more frequently in the XbaI GA genotype (p=0.025), while XbaI AA genotype was associated with dysmenorrhea in patients with FMS (p=0.041). CONCLUSION: Our results indicate that ESR1 PvuII/XbaI variants are possibly effective in the development of FMS and some clinical features.

VNTR Variant of the eNOS Gene and its Relationship with Osteoporosis in Postmenopausal Turkish Women.

BACKGROUND: Osteoporosis (OP) is the most common type of systemic bone disease characterized by low bone mass and micro-structure deterioration of bone tissue, with a consequent increase in bone fragility and fracture risk. Nitric oxide (NO), produced by the enzyme endothelial nitric oxide synthase (eNOS) in endothelial cells, has considerable effects on bone cell function. The objective of this case-control study was to investigate the potential association between the eNOS gene Variable Number Tandem Repeat (VNTR) variant and susceptibility of OP, in Turkish postmenopausal female patients. METHODS: One hundred and fifty female patients and 100 age-matched healthy females were enrolled in the present study. The eNOS gene VNTR variant was genotyped with a polymerase chain reaction (PCR) method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: The mean age of the patients was 60.32±8.65 years. It was found that the eNOS VNTR variant genotype and allele frequencies were not significantly different between the patient and control groups (p>0.05).

Analysis of Interleukin-1 Receptor Antagonist Variable Number Tandem Repeat Variant in Recurrent Aphthous Stomatitis.

BACKGROUND/AIMS: Recurrent aphthous stomatitis (RAS) is one of the common oral inflammatory diseases. As immunological and genetic factors have been held responsible for the pathogenesis of RAS, the objective of this study was to determine whether the interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) variant is a risk factor for the development of RAS in Turkish patients and to define its contribution to the increased risk. METHODS: The IL-1Ra VNTR variant was evaluated in 169 RAS patients and 171 healthy controls by the polymerase chain reaction (PCR) method. RESULTS: No statistically significant difference was found in the genotype distributions and allele frequencies of IL-1Ra VNTR variant between RAS patients and healthy controls. CONCLUSION: Lack of association between IL-1Ra VNTR variant and RAS could indicate that IL-1Ra has no significant role in the pathophysiology of RAS. However, it still appears to be very worthwhile to continue to search for cytokine gene variants in order to predict the development of such disease.

A Case-Control Study Investigating the Effect of MTHFR C677T Variant on Performance of Elite Athletes.

OBJECTIVE: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects elite athletic performance. METHODS: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. CONCLUSION: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

A Relationship between Endothelial Nitric Oxide Synthetase Gene Variants and Substance Use Disorder.

BACKGROUND: Addictive substances are known to result in oxidative stress (OS). OS enhances the generation of free radicals and reactive oxygen species (ROS) and reduces antioxidant capacity. Peroxides and oxygen radicals, including hydrogen peroxide and superoxide and radical nitrogen species, including nitric oxide (NO), are parts of the ROS. Gene variants of the endothelial nitric oxide (eNOS) affect the plasma levels of NO. This study aimed to investigate whether there was an association between eNOS variants and substance use disorders (SUDs) risk in the Turkish population. METHODS: Two eNOS variants (G894T and 27 bp VNTR 4b/a in intron 4) were examined in 216 SUD patients and 140 healthy controls. The eNOS variants were assessed with the PCR based on the RFLP analysis. Since the patient group consisted only of men, the control group was examined as a mixed and male-only. RESULTS: The eNOS G894T homozygous T/T genotype revealed a significant association with susceptibility to SUD. The patients carrying T/T genotype had SUD risk 1.054 times as much as the controls and male controls had (p=0.004 and p=0.038, respectively). eNOS 4a/4a genotype increased in patients as compared to male controls (p=0.048). The homozygous 4b/4b genotype was higher in the male control group than in SUD patients (p=0.029). eNOS VNTR 4a allele was more prevalent in the patients than in both controls and male controls (p=0.026 and p=0.0033, respectively). CONCLUSION: This study is one of the first studies investigating the relationship between two eNOS gene variants and SUD in our country. Our findings show that eNOS G894T and VNTR variants may be the significant risk factor for SUDs in Turkish subjects.

Role of MIF-173G/C and Mbl2 Codon 54A/B Variants in the Risk of Multiple Myeloma: An Association Study.

BACKGROUND: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. OBJECTIVE: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. METHODS: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. RESULTS: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF- 173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon 54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). CONCLUSION: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.

The possible role of CCR5Δ32 mutation in Crimean-Congo hemorrhagic fever infection.

Crimean-Congo hemorrhagic fever infection (CCHF) is a viral zoonosis. The pathogenesis of this disease has not been established so far, however, cytokines account for its progression and outcome. The aim of the present study is to investigate the association between chemokine receptor 5 (CCR5) gene Δ32 mutation and pathogenity, severity, and mortality of CCHF. This case-control study included 133 CCHF patients diagnosed by detection of CCHV RNA positivity and 97 healthy control subjects. CCR5 gene Δ32 mutation analyzed by polymerase chain reaction (PCR) method. The results were compared by using SPSS 16.0 and WINPEPI software's. The genotype distribution and allele frequency of the CCR5Δ32 were statistically different between the patients and the control group (P = 0.017; OR: 4.98 95% CI = 1.65-14.99 and P = 0.019; OR:4.76 95%CI = 1.30-17.50, respectively). CCR5/CCR5 (W/W) genotype and W allele of CCR5 gene were more common in patient group than in controls. There was no significant difference in severe and mild cases with regard to genotype distribution and allele distribution of CCR5Δ32 mutation (P >0.05). These results suggest that the CCR5 gene and its product might play a role in the pathogenesis of CCHF disease. Future studies will help us to uncover the exact role of CCR5 in the pathogenesis and prognosis of CCHF and to treat the disease.