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 a circadian rhythm gene (PER3) VNTR variant in Turkish athletes.

OBJECTIVE: Circadian rhythmicity has been shown to contribute to the regulation of key physiological and cognitive processes related to performance. The period homolog 3 (PER3) is expressed in a circadian pattern in the suprachiasmatic nucleus. Therefore, in this study, we aimed to evaluate the role of the variable tandem repeat (VNTR) variant of the PER3 gene in athletic performance in the Turkish population. METHODS: This study included 223 subjects, which consisted of 123 athletes and 100 sedentary controls. Blood samples were drawn from all subjects. DNA was extracted from whole-blood samples. The PER3 VNTR variant was genotyped using the polymerase chain reaction-restriction method (PCR). The results of the analyses were evaluated for statistical significance. RESULTS: The mean ages of athletes and controls were 22 ± 2.814 and 23 ± 3.561, respectively. Endurance athletes in the group were 21.1%, and sprint athletes were 78.9%. There was no statistical significance in terms of PER3 VNTR genotype distribution or allele frequency. In the recessive model, a statistically significant association was observed when the athletes were compared with the controls according to 4/4 + 4/5 versus 5/5 genotype (p = 0.020). CONCLUSION: In this case-control study, for the first time in our country, we obtained findings suggesting that the PER3 VNTR variant may affect sports performance in the Turkish population. Results need to be replicated in different ethnic and larger samples.

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.

Macrophage Migration Inhibitory Factor -173GC Variant Might Increase the Risk of Behçet's Disease.

OBJECTIVE: The aim of the present study was to investigate any possible association between the macrophage migration inhibitory factor (MIF) -173GC variant and Behçet's disease (BD) in a group of Turkish patients. SUBJECTS AND METHODS: A total of 111 patients with BD and 100 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral lymphocytes. The MIF -173GC variant was genotyped using polymerase chain reaction restriction fragment length polymorphism. The allele and genotype frequencies of patients and controls were compared using the χ2 test. RESULTS: A statistically significant difference in the distribution of the genotype was observed between BD patients and healthy controls. The homo-genotype CC was more prevalent in the patient group compared to the control group (p = 0.008, OR: 0.24, 95% Cl: 0.05-0.78). A significant association was observed when the patients were compared with the controls according to GG + GC versus CC ge-notypes (p = 0.003, OR: 1.21, 95% CI: 0.06-0.063). Allele frequencies of the MIF -173GC variant did not show any statistically significant difference between patients and controls. CONCLUSION: In this study, we conclude that the CC ge-notype of the MIF -173GC variant may be a risk factor in the pathogenesis of BD in the Turkish population. However, further studies with larger samples are needed to address the exact role of this variant in BD.

PPAR-α and PPARGC1A gene variants have strong effects on aerobic performance of Turkish elite endurance athletes.

The aim of this study was to investigate the effect of PPAR-α intron 7G>C and PPARGC1A gene Gly482Ser polymorphisms on aerobic performance of elite level endurance athletes. This study was carried out on 170 individuals (60 elite level endurance athletes and 110 sedentary controls). Aerobic performance of athletes and sedentary control groups were defined by maximal oxygen uptake capacity. DNA was isolated from peripheral blood using GeneJet Genomic DNA Purification kit. Genotyping of the PPAR-α intron 7G>C and PPARGC1A Gly482Ser polymorphisms was performed using PCR-RFLP methods, and statistical evaluations were carried out using SPSS 15.0. Mean age of athletes were 21.38 ± 2.83 (18-29) and control mean age were 25.92 ± 4.88 (18-35). Mean maximal oxygen consumption of athletes were 42.14 ± 7.6 ml/(kg min) and controls were 34.33 ± 5.43 ml/(kg min). We found statistically significant differences between the athlete and control groups with respect to both PPAR-α and PPARGC1A genotype distributions (p = 0.006, <0.001, respectively) and allele frequencies (<0.001, <0.001, respectively). Additionally, when we examined PPAR-α and PPARGC1A genotype distributions according to the aerobic performance test parameters, we found a statistically significant association between velocity, time and maximal oxygen consumption and PPAR-α and PPARGC1A genotypes (p < 0.001). To our knowledge, this is the first study in Turkey examined PPAR-α intron 7G>C and PPARGC1A Gly482Ser gene polymorphisms in elite level endurance athletes. Our results suggest that PPAR-α and PPARGC1A genes have strong effect on aerobic performance of elit level athletes.

Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis.

OBJECTIVE: Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. METHODS: The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively). CONCLUSIONS: Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA.