Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease

Abstract

Abstract. The aim of this study was to assess the association of 27-bp variable number tandem repeat (VNTR) polymorphism in intron 4 and G894T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene with Legg-Calvé-Perthes disease (LCPD), and to provide a scientific basis for further research into the pathogenic mechanism. A total of 80 patients with LCPD and 100 healthy subjects were recruited in this case-control study. The 27-bp VNTR and G894T polymorphisms of the eNOS gene were genotyped using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, followed by agarose gel electrophoresis and DNA sequencing. Allelic and genotypic frequencies were computed in the two groups and subjected to statistical analysis. For the 27-bp VNTR polymorphism, individuals with LCPD showed a higher frequency of the ab genotype [27.5 vs. 14%; odds ratio (OR), 2.33; 95% confidence interval (CI), 1.10-4.92; P=0.024]. For the G894T polymorphism, the LCPD case group showed a higher frequency of the heterozygous genotype GT than the healthy control group (35 vs. 17%; OR, 2.67; 95% CI, 1.33-5.36; P=0.005). The results indicate that these eNOS gene polymorphisms may be a risk factor for LCPD. The 27-bp VNTR polymorphism in intron 4 and G894T polymorphism in exon 7 may be involved in the etiology of LCPD.

Research Article Infertility caused by an association between <em>Arg72Pro</em> polymorphism of the <em>p53</em> gene and <em>Glu298Asp</em> of the <em>eNOS</em> gene in patients with endometriosis

“…According to Najafi et al (2013), women with infertility showed a higher eNOS expression only in the uterine luminal epithelium compared to the control group. Moreover, studies reveal the increased expression of eNOS in the endometrium throughout the menstrual cycle in patients with endometriosis compared to women without endometriosis, and higher levels of NO in the ectopic endometrium compared to the eutopic endometrium (Kim et al, 2009;Seckin et al, 2016;Zhao et al, 2016). Pena et al (2000) demonstrated in his study that there is a great difficulty to obtain a genetically representative sample of the Brazilian population.…”

“…Nitric oxide (NO) is a multifunctional biomolecule synthesized from L-arginine by three isoenzymes of Nitric Oxide Synthase (NOS): neuronal nitric oxide synthase (nNOS), induced nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) (Seckin et al, 2016;Zhao et al, 2016). Nitric oxide is responsible for the regulation of vasodilation, exerting its effect by regulating the migration of endothelial cells, and it takes part in several physiological processes including angiogenesis, thrombosis, coagulation and fibrinolysis (Zhao et al 2016).…”

“…Nitric oxide (NO) is a multifunctional biomolecule synthesized from L-arginine by three isoenzymes of Nitric Oxide Synthase (NOS): neuronal nitric oxide synthase (nNOS), induced nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) (Seckin et al, 2016;Zhao et al, 2016). Nitric oxide is responsible for the regulation of vasodilation, exerting its effect by regulating the migration of endothelial cells, and it takes part in several physiological processes including angiogenesis, thrombosis, coagulation and fibrinolysis (Zhao et al 2016). The eNOS is a gene located on chromosome 7 (7q35-q36), with 26 exons and 25 introns and encodes a protein of 1,203 amino acids (Zhao et al, 2016); eNOS is an important pro-angiogenic factor, associated with the development of endometriosis since angiogenesis is needed for ectopic endometrial tissue to survive outside the uterus (Kim et al, 2009).…”

“…The most widely studied and functionally relevant polymorphism associated with eNOS is G894T-Glu298Asp (rs1799983) in codon 298 of exon 7, which corresponds to a variable number tandem repeat (VPNR). This type of eNOS polymorphism promotes a point mutation from guanine into thymine leading to a change in the expected enzymatic activity promoted by the eNOS protein (Zhao et al, 2016). Another polymorphism, T786C (rs2070744), changes thymine into cytosine at position 786 of the 5'-flanking region of the gene.…”

Association of Nitric Oxide Levels and Endothelial Nitric Oxide Synthase G894T Polymorphism with Coronary Artery Disease in the Iranian Population

“…Analysis of eNOS G894T polymorphism was conducted by polymerase chain reaction (PCR)-restriction fragment length polymorphism method as previously described [ 15 ]. The sequences of primers used for PCR reaction were as follows, forward: 5′-AAGGCAGGAGACAGTGGATGG-3′ and reverse: 5′-CCCAGTCAATCCCTTTGGTGCT CA-3′.…”