Cyclooxygenase-2 Gene Polymorphisms Research Articles

Endometrial receptivity defects MUC-1 and COX-2 polymorphisms in endometriosis.

The endometrium produces MUCIN-1 (MUC-1) and cyclooxygenase-2 (COX-2), which are essential for implantation. MUC-1 is required for adhesion, while COX-2 is necessary for decidualization. Variations or polymorphisms in MUC-1 and COX-2 can lead to changes in endometrial receptivity. This study investigated the relationship between MUC-1 and COX-2 polymorphisms and endometrial receptivity in endometriosis patients. Blood DNA samples were collected from 35 patients with endometriosis and 32 healthy patients between days 19 to 24 of their menstrual cycle (secretory phase). MUC-1 polymorphism was determined using the Amplification Refractory Mutation System (ARMS), and COX-2 gene polymorphism was assessed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The frequency distribution of gene polymorphisms between the two groups was compared using bivariate analysis. There were seven genotypic combinations of MUC-1 and COX-2: AAGC; AAGG; GACC; GAGC; GAGG; GGGC; GGGG. The AAGC genotype combination test was significant, with an OR=6.43 (95% CI:1.09-7.62) and p=0.01. In conclusion, combining MUC-1 and COX-2 (AAGC) genotypes results in endometrial receptivity defects in endometriosis.

Plasma Cyclooxygenase-2 as a Potential Biomarker for Early Diagnosis of Kawasaki Disease

Background: Previous research demonstrated the association between cyclooxygenase-2 (COX-2) gene polymorphisms and susceptibility to Kawasaki disease (KD). This study aims to detect the plasma concentration of COX-2 in different phases of KD patients and evaluate the relationship between COX-2 level and coronary artery lesion formation, therapeutic response to intravenous immunoglobulin. Methods: Plasma COX-2 levels were measured by enzyme-linked immunosorbent assay in KD patients during the acute (a-KD, n = 52), subacute (s-KD, n = 46), and convalescent (c-KD, n = 43) phase. Results: The concentration of COX-2 in the a-KD group was significantly higher than that in the s-KD, c-KD, healthy control or febrile control group, respectively. There was no difference in the levels of COX-2 between the KD with or without coronary artery lesion subgroups, intravenous immunoglobulin resistant, and sensitive subgroups in the a-KD group, respectively. Conclusions: The plasma concentration of COX-2 might be a novel potential biomarker of acute KD.

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

Association between COX-2 Gene Polymorphism and Susceptibility to Colon and Rectal Cancer

Elevated Levels of PGE2-Metabolite in Cerebrospinal Fluid and Cox-2 Gene Polymorphisms in Patients with Chronic, Post Cholecystectomy Pain and Visceral Hyperalgesia Compared to Healthy Controls. A Hypothesis-Generating Pilot Study.

Chronic, abdominal pain remains a problem in a subset of patients after cholecystectomy. The cause is often obscure but central sensitization may be an important component and could theoretically be mediated by spinal PGE2, which is regulated by several cytokines. The aim of the study was to examine cerebrospinal fluid (CSF) of participants with post cholecystectomy syndrome and healthy volunteers for signs of PGE2 and cytokine mediated central sensitization. In phase 1 of the study, 83 subjects were included for DNA analysis, eight of these subjects with post cholecystectomy syndrome. We examined the SNPs rs5275, rs16944 and rs1800795 from the Cox-2, IL-1β and IL-6 genes respectively. In phase 2 of the study, we examined concentrations of PGE2-metabolite (PGEM), IL-1β and IL-6 in CSF and plasma from 6 patients with post cholecystectomy syndrome and visceral hyperalgesia and 11 pain free volunteers. We found a significant difference in distribution of the rs5275 SNP of the Cox-2 enzyme (CT-genotype=88% in pain group, 45% in pain free group, TT-genotype=0 in pain group, 41% in pain free group, p=0.05) but not in the other SNPs. PGEM, but not IL-6, was significantly elevated in CSF of the pain group (3.6 pg/mL, sd=1.9 vs 2.1 pg/mL, p=0.03), IL-1β was undetectable. We found elevated PGEM levels in CSF of patients with post cholecystectomy syndrome and visceral hyperalgesia, suggesting a central, possibly inflammatory component to the pain, and overrepresentation of the CT-genotype in the rs5275 SNP in the Cox2 gene, suggesting overexpression of Cox2 as a possible cause for elevated PGEM levels.

Detection of cyclooxygenase -2 gene polymorphism among Sudanese women with recurrent spontaneous abortion in Khartoum state, Sudan in 2021

Background: Recurrent spontaneous abortion is a health issue that occurs in about 1 — 5% of all women of reproductive age. Experimental evidence suggests that COX-2 plays an important part in blastocyst implantation but rarely is the role of COX-2 recognized in recurrent spontaneous abortions. Methods: This is a descriptive analytical case-control hospital study that was carried out at the Research Laboratory of the National Center for Neuroscience in Khartoum, Sudan from April to September 2021. The study intended to detect cyclooxygenase-2 gene polymorphism among Sudanese women with RSA. Women with more than three recurrent miscarriages were included in this study as the sample cases and women with no history of abortion at child-bearing age were included as the controls. From each of the subjects, three ml of venous blood was gathered in sterile containers with Ethylene Diamine Tetra-acetic Acid (EDTA). The DNA was isolated using the standard phenol chloroform extraction method. The COX-2 gene was amplified using conventional PCR. The products of the PCR were sent to the Macro Gene Laboratory for sequencing. Results: In the current research, 230 bp of C0X-2 gene was disclosed using gel electrophoresis after PCR. The results for the detected gene from all subjects were analyzed. The X2-test showed that there were significant differences in the gene expression and distribution between the case and control groups (p value 0.001). The sequence results analysis showed that there was a change in C>A at Location 1:633149 (Rs1481253765) and a change in G> T cDNA position 427 at Location 1:633183 (Rs1232472838). Conclusion: This study showed that there was a consequential difference in the COX-2 allele between the case and control groups. The mutant gene is a potential new clarification point regarding recurrent spontaneous abortion in several cases.

Investigation of Cyclooxygenase-2 Gene Polymorphism in Patients with Gastric Cancer and Healthy Individuals in Northern Iran

Background: Gastric cancer is one of the most common types of cancer in the world. Cyclooxygenase-2 (COX-2) is a pro-inflammatory enzyme and an important mediator of tumor cell proliferation and angiogenesis. Objectives: The aim of this study was to investigate the relationship between COX-2 gene polymorphism and the risk of developing gastric cancer. Methods: This case-control study was carried out on 150 patients with gastric cancer and 150 healthy individuals. Genomic DNA was extracted using a modified method of protein precipitation at high salt concentrations. Polymorphisms of the COX-2 gene were investigated by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: In this study, the frequency of GG genotype and CC genotype was significantly higher in patients with gastric cancer and healthy individuals, respectively (P < 0.05). However, the frequency of CC genotype did not significantly differ between the 2 study groups. Conclusions: We demonstrated that the homozygous GG genotype of COX-2 is significantly more frequent in patients with gastric cancer compared to healthy individuals. This could indicate the possible role of COX-2 in the development or progression of gastric cancer.

Association of IL-1β, NLRP3, and COX-2 Gene Polymorphisms with Autoimmune Thyroid Disease Risk and Clinical Features in the Iranian Population.

Background Grave's disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune diseases of the thyroid gland in which genetic predisposition plays a major role in their development. Currently, the role of NLRP3 inflammasome and COX-2 has been documented in many autoimmune diseases. The purpose of the study is to delineate the impact of IL-1β (rs1143634), NLRP3 (rs3806265), and COX-2 (rs2745557) gene polymorphisms in the development of GD and HT. Methods A total of 256 newly diagnosed patients with autoimmune thyroid disease (135 patients with HT and 121 GD patients) as case groups and 145 controls were included in the study. Results Recessive and overdominant models showed a significant association between IL-1β rs1143634 SNP and HT development risk. The frequency of TT genotype and T allele of IL-1β rs1143634 SNP in the control group was significantly higher than the GD group. There was no significant association between NLRP3 rs3806265 polymorphism and HT and GD development. The frequency of GA genotype of COX-2 (rs2745557) in the control group was significantly higher than that in the HT group. There was no significant association between COX-2 rs2745557 genotypic and allelic distribution and GD development risk. The results revealed a significant relationship between some clinical features of HT and GD groups and SNPs studied. Conclusion The results manifest the significant impact of IL-1β rs1143634 and COX-2 (rs2745557) SNPs and HT development and IL-1β rs1143634 SNP on GD occurrence risk. Furthermore, a significant relationship was observed between some clinical features of HT and GD groups and studied SNPs.

Genetic Polymorphisms of Cyclooxygenase2 (COX2) Gene in Eastern Indian Chronic Periodontitis Patients

ABSTRACT This present study is aimed to find out the association of Cyclooxygenase2 or COX2 gene polymorphisms such as COX2-765C/G (rs20417), COX2-1195A/G (rs689466) and COX2+8473C/T (rs5275) gene polymorphism with chronic periodontitis in eastern Indian population. A case control study had been performed with a total of 357 participants where 157 identified as patients with chronic periodontitis and the rest 200 were taken as control population. All statistical analysis was performed in SNPassoc, Haploview, MDR 3.0.2 version software packages. The studied COX2 gene polymorphisms are genotypically significantly associated with studied CP population (de0.01). The mutant alleles of three polymorphisms COX2-765C/G, COX2-1195A/G and COX2+8473C/T are significantly associated to the increased susceptibility of CP (OR= 2.01, 95%CI= 1.475- 2.754, p<0.0001; OR= 1.7, 95%CI= 1.249-2.331, p=0.0008; OR= 2.2, 95%CI= 1.61-3.014, p<0.0001 respectively). There are four haplotypes CCA, TGG, TCG and CCG found to be related to the increasing risk of CP. All three COX2 gene polymorphisms are found to be significantly associated with chronic periodontitis increased susceptibility in studied population.

Cyclooxygenase-2 Gene Polymorphisms –765G>C and –1195A>G and Mycosis Fungoides Risk

Background: Cyclooxygenase-2 (COX-2) is an inducible modulator of inflammation that acts through increasing prostaglandin levels and has been described as a major mediator linking inflammation to cancer. Previous studies supported that COX-2–765G>C and –1195A>G polymorphisms were associated with increased risk of several solid tissue cancers as well as some hematological malignancies. Objective: The aim of the study was to elucidate the association between functional COX-2 genotypes (–765G>C and –1195A>G) polymorphisms and the risk of developing mycosis fungoides (MF). Methods: This was a hospital-based, case-control study of 70 MF patients and 100 MF-free controls. We genotyped COX-2 –1195A>G, –765G>C, and –8473T>C polymorphisms by using the PCR-restriction fragment length polymorphism method. Results: The AA genotype in the COX-2 –1195A>G gene polymorphism and the GC genotype in the COX-2 −765G>C gene were significantly more frequent among MF patients compared to controls (p< 0.001 and p = 0.002, respectively). Conclusion: The ­results indicate a possible role of COX-2 genes in the pathogenesis of MF. These novel findings may allow for notable future advances, as it will enable the identification of the ­individuals most susceptible to MF.

Association of a genetic variant (rs689466) of Cyclooxygenase-2 gene with chronic periodontitis in a sample of Iraqi population

Background: periodontitis is a chronic inflammatory disease causing destruction of the tooth supporting structures, initiated by dental plaque and modified by environmental and genetic risk factors. Cyclooxygenase-2 (COX-2) enzyme is responsible for the production of prostaglandin E2, an important mediator in the chronic periodontitis (CP) pathogenesis. Polymorphisms in COX-2 gene have linked to CP in different populations. Aim: To study the association between Cyclooxygenase-2 single nucleotide polymorphism rs689466 (-1195A/G SNP) and chronic periodontitis in a sample of Iraqi population. Methods: One hundred Iraqi subjects divided into two groups: case group consisted of 70 CP patient (35 males and 35 females) with age range 30-55 years, and control group consisted of 30 racially matched healthy subjects (15 males and 15 females) with age range 30-50 years. Clinical periodontal parameters including plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL) were recoded for all participants. 3ml of venous blood was collected from each participant for isolating genomic DNA. Genotyping of the rs689466 in COX-2 gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequency of G allele carriers was significantly more prevalent in the case group compared to control group (P= 0.041), and allele G was associated with greater susceptibility for chronic periodontitis compared to allele A (OR=1.4). Conclusion: COX-2 (rs689466) polymorphism may be associated with increased chronic periodontitis susceptibility.

Correlation analysis between COX-2 gene polymorphism and eclampsia.

The aim of this study was to investigate the expression of cyclooxygenase-2 (COX-2) in eclampsia patients, and to explore the correlation between COX-2 polymorphism and incidence of eclampsia. From January 2016 to January 2018, a total of 280 pregnant women diagnosed in the Obstetrics and Gynecology Department of our hospital were selected for this study. All patients were divided into two groups, including normal pregnancy control group (n=120) and eclampsia group (n=160). The expression of COX-2 in placenta and umbilical cord tissues of eclampsia group and normal group was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting and immunohistochemical staining. The single-nucleotide polymorphisms (rs1526172, rs1245231 and rs2198532) in the promoter region of the COX-2 gene were typed via conformation difference gel electrophoresis. Whether the distribution frequency of COX-2 genotypes met Hardy-Weinberg equilibrium law was detected via the Chi-square test. Meanwhile, the correlation between COX-2 alleles and gene polymorphisms and the incidence of eclampsia was analyzed. The messenger ribonucleic acid (mRNA) and protein expression levels of COX-2 in the eclampsia group were significantly higher than those of the normal group (p<0.05). According to the analysis, three polymorphisms of COX-2 gene were all in line with Hardy-Weinberg equilibrium distribution (p>0.05). Gene association analysis revealed that only polymorphisms (rs1526172 and rs1245231) and alleles were correlated with the incidence of eclampsia (p<0.05). However, polymorphism rs2198532 and alleles were not correlated with the incidence of eclampsia (p>0.05). Rs1526172 and rs1245231 in the promoter region of COX-2 are correlated with the incidence of eclampsia, while rs2198532 has no correlation with eclampsia.

Correlation between COX-2 gene polymorphism and susceptibility to nasopharyngeal carcinoma.

The aim of this study was to investigate cyclooxygenase-2 (COX-2) gene polymorphism in peripheral blood cells of patients with nasopharyngeal carcinoma (NPC) and normal people, and to explore the correlation between polymorphism and the occurrence of NPC. The genotype and allele distributions of gene loci COX-2-899 (G/C) and COX-2-1195 (G/A) in peripheral blood of 56 normal people and 114 NPC patients were analyzed via reverse transcription-polymerase chain reaction (RT-PCR). The genetic equilibrium was detected by TaqMan genotyping technique. Meanwhile, the risk factors for NPC were analyzed via multivariate logistic regression analysis. Subsequently, the effects of risk factors, clinical features, and gene polymorphism of NPC on the prognosis and survival of patients were analyzed using univariate and multivariate COX regression analysis. Finally, the correlation of smoking, Epstein-Barr (EB) virus infection and COX-2-1195 gene polymorphism with NPC was explored via χ2-test. There was a significant difference in the genotype and allele distributions at COX-2-1195 (G/A) between the two groups (p<0.05). However, no significant differences were observed at COX-2-899 (G/C) between the two groups (p>0.05). According to the results of univariate and multivariate COX regression analysis, smoking and EB virus infection were risk factors for NPC (p<0.05). The χ2-test indicated that there was an evident gene polymorphism at COX-2-1195 in smokers and EB virus-infected people compared to non-smokers and non-infected people (p<0.05). COX-2-1195 gene polymorphism is associated with susceptibility to NPC. Smoking and EB virus infection are major risk factors for NPC, both of which can affect COX-2-1195 gene polymorphism.

The Relationship of COX-2 Gene Polymorphisms and Susceptibility to Kawasaki Disease in Chinese Population

ABSTRACTBackground: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children, and it can result in coronary artery lesions. Cyclooxygenase-2 (COX-2) is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of several prostaglandins. The aim of this study was to examine the association between COX-2 gene polymorphisms and susceptibility to KD.Methods: A total of 276 subjects (136 KD and 140 controls) were recruited. The analysis of two single nucleotide polymorphisms rs689466 (−1195G/A) and rs20417 (−765G/C) was respectively detected with polymerase chain reaction sequence-based typing methods.Results: Polymorphisms of rs689466 were significantly different between the normal controls and KD patients (χ2 = 6.070 and 5.435, both p < 0.05). The frequencies of AA genotype and A allele of rs689466 in Kawasaki disease group were higher than that of control group (χ2 = 4.832, p = 0.028, OR = 1.832, 95%CI = 1.064–3.124; χ2 = 5.435, p = 0.028, OR = 1.491, 95%CI = 1.065–2.088).Conclusion: This study provides the first evidence supporting an association between COX-2 gene polymorphisms and susceptibility of KD. The AA genotype and A allele of rs689466 confer predisposing factors to KD.

PTGS2 polymorphism rs689466 favors breast cancer recurrence in obese patients.

Breast cancer is the leading cancer among women, and its increasing incidence is a challenge worldwide. Estrogen exposure is the main risk factor, but obesity among postmenopausal women has been shown to favor disease onset and progression. The link between obesity and mammary carcinogenesis involves elevated estrogen production and proinflammatory stimuli within the adipose tissue, with activation of the cyclooxygenase-2 pathway. Here, we evaluate the impact of the four most common cyclooxygenase-2 gene polymorphisms (rs689465, rs689466, rs20417 and rs20417), in combination with obesity, on the risk of breast cancer progression in a cohort of Brazilian breast cancer patients (N = 1038). Disease-free survival was evaluated using Kaplan-Meier curves, with multivariate Cox proportional hazards regression models for calculation of adjusted hazard ratios (HRadj). Obesity did not affect disease progression, whereas rs689466 variant genotypes increased the recurrence risk among obese patients (HRadj = 2.5; 95% CI = 1.4-4.3), either for luminal (HRadj = 2.2; 95% CI = 1.1-4.2) or HER2-like and triple-negative tumors (HRadj = 3.2; 95% CI = 1.2-8.5). Likewise, the haplotype *4, which contains variant rs689466, was associated with shorter disease-free survival among obese patients (HRadj = 3.3; 95% CI = 1.8-6.0), either in luminal (HRadj = 3.5; 95% CI = 1.6-7.3) or HER2-like and triple-negative (HRadj = 3.1; 95% CI = 1.1-8.9) tumors. Such deleterious impact of variant rs689466 on disease-free survival of obese breast cancer patients was restricted to postmenopausal women. In conclusion, cyclooxygenase-2 genotyping may add to the prognostic evaluation of obese breast cancer patients.

Cyclooxygenase-2 gene polymorphisms and susceptibility to hepatocellular carcinoma: A meta-analysis based on 10 case-control studies.

The association between cyclooxygenase-2 (COX-2) gene polymorphisms and hepatocellular carcinoma (HCC) has been widely reported, but the results are still controversial. To clarify the effect of COX-2 -1195G/A (rs689466), -765G/C (rs20417), and +8473T/C (rs5275) polymorphisms on HCC risk, a meta-analysis was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature, Wanfang, and Chinese National Knowledge Infrastructure databases were systematically searched to identify potential studies published up to October 10, 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. A total of eight studies with 2060 HCC cases and 2610 controls for -1195G/A, six studies with 1295 cases and 2193 controls for -765G/C, and four studies with 1477 cases and 1747 controls for +8473T/C were included in this meta-analysis. Overall, the COX-2 -1195G/A, and +8473T/C polymorphisms were both significantly associated with an increased risk of HCC (rs689466 GA + AA vs. GG: OR = 1.390, P = 0.006, 95% CI: 1.099-1.759, I2 = 50.7%, Pheterogeneity = 0.048; rs5275 CC vs. TT + TC: OR = 1.484, P = 0.041, 95% CI: 1.017-2.165, I2 = 0.0%, Pheterogeneity = 0.416). In the subgroup analyses stratified by ethnicity, the COX-2 -1195G/A, -765G/C, and +8473T/C were all associated with an increased HCC risk in Asian populations (rs689466 A vs. G: OR = 1.346, P = 0.001, 95% CI: 1.137-1.595, I2 = 0.0%, Pheterogeneity = 0.869; rs20417 CC vs. GG + GC: OR = 3.069, P = 0.013, 95% CI: 1.265-7.447; rs5275 CC vs. TT + TC: OR = 1.626, P = 0.020, 95% CI: 1.079-2.452, I2 = 0.0%, Pheterogeneity = 0.495). Our meta-analysis suggests that -1195G/A, -765G/C, and +8473T/C in COX-2 may contribute significantly to HCC risk.

Study of the relation between two common cyclooxygenase 2 gene polymorphisms with risk of developing and subtypes of vitiligo in Egyptian patients

Genetic factors play an important role in the pathogenesis of vitiligo. Cyclooxygenase 2 (COX2) gene induced by ultraviolet radiation controls the synthesis of prostaglandins, which are are found to be beneficial in treating vitiligo. COX2 gene polymorphism has been previously evaluated in Chinese population. We aimed to study the relation between two common COX2 gene polymorphisms with vitiligo and its subtypes amongEgyptian patients. This study included 200 participants (100 vitiligo patients and 100 healthy controls). COX2-765G/C and -1195A/G gene polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction analysis and the results were compared between the two groups and among different subtypes of vitiligo. Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group. Regarding COX2-765G/C genotypes, GG genotype was more frequent among patients with vitiligo [84 (84%)] compared to controls [63 (63%)] (P = 0.001). GC genotype was significantly less frequent [15 (15%)] among patients compared to controls [32 (32%)] (P = 0.005). Generalized and segmental types of vitiligo also showed no significant difference in the frequency of COX2-765G/C genotypes compared with controls. Being a pilot study, a relatively small number of participants were included. COX2-1195A/G gene polymorphism is not associated with the risk of developing vitiligo or with vitiligo subtypes. COX2-765 GG genotype is associated with vitiligo, especially of the generalized type.

COX2 and NOS3 gene polymorphisms in women with gestational diabetes.

Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnancy. Low-grade inflammation plays an important role in the pathogenesis of this disorder. The present study aimed to examine the association between COX2 (rs6681231) and NOS3 (rs1799983 and rs2070744) gene polymorphisms and GDM. The study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28weeks of gestation. We observed an increased frequency of COX2 rs6681231 CC and GC genotype carriers among women with GDM (CC+GC versus GG, odds ratio=1.55, 95% confidence interval=1.01-2.36, p=0.043; C versus G, odds ratio=1.59, 95% confidence interval=1.10-2.30, p=0.013). There were no statistically significant differences in the distribution of NOS3 rs1799983 and rs2070744 between GDM and healthy women. Moreover, among women treated with insulin, we observed an increased frequency of COX2 rs6681231 CC and NOS3 rs1799983 TT genotype carriers. The results of the present study suggest that the CC genotype of the COX2 rs6681231 polymorphism is associated with an increased risk of GDM and the need for insulin therapy, whereas the TT genotype of the NOS3 rs1799983 polymorphism may be associated with the need for insulin therapy in women with GDM.

Cyclooxygenase-2 gene polymorphisms and susceptibility to colorectal cancer in a Brazilian population.

Multi-ethnicity of Brazilian population displays high levels of genomic diversity. Polymorphism may detect people at higher risk of developing cancer, distinctive response to treatment, and prognosis. Cyclooxygenase-2 (COX-2) is induced in response to growth factors and cytokines, and is expressed in inflammatory diseases, precancerous lesions and colorectal cancer (CRC). The aim of this study was to evaluate the influence of COX-2 -1195A > G and 8473T > C polymorphisms as a risk factor of developing CRC. We evaluated COX-2 Single Nucleotide Polymorphism (SNP) of 230 CRC patients and 196 healthy controls by Real-Time Polymerase Chain Reaction. Populations were in Hardy-Weinberg equilibrium (HWE), except for control group of 8473T > C SNP. The frequencies were similar in both groups for genotypes and haplotypes. There was no association between studied polymorphisms and risk of CRC. The gene polymorphisms studied do not participate in the genetic susceptibility to CRC in a Brazilian population.

Cyclooxygenase-2 (COX-2) polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population

Background: Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population.Methods: A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the SNaPshot genotyping method. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups.Results: Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs. AA + AG) (OR = 1.74, 95% CI: 1.098–2.755, p = .018). Although no statistical differences were identified of rs689466 between the two groups by allele model (p = .098) or homozygous model (p = .084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort.Conclusions: To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population.

Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer.

The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and metastasis in certain types of cancer. Nevertheless, the prognostic value of COX-2 overexpression and its polymorphisms in patients with non-small cell lung cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was to investigate the association between the three most commonly studied COX-2 gene polymorphisms (−1195 G/A, −765 G/C and 8473 T/C) with COX-2 expression and lung cancer risk in a Brazilian cohort. In the present hospital based, case-control retrospective study, 104 patients with NSCLC and 202 cancer free control subjects were genotyped for −1195 G/A, −765 G/C and 8473 T/C polymorphisms using allelic discrimination with a reverse transcription quantitative polymerase chain reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors from 34 patients with NSCLC. The results revealed that COX-2 expression levels were higher in tumor tissue compared with normal lung tissue. However, this overexpression of COX-2 was not associated with the patient outcome, and furthermore, none of the analyzed polymorphisms were associated with the risk of developing lung cancer, COX-2 overexpression, or the overall survival of the patients with NSCLC. Taken together, the findings described in the present study do not support a major role for COX-2 polymorphisms and COX-2 overexpression in lung carcinogenesis within the Brazilian population.