Cyclooxygenase-2 Polymorphisms Research Articles

Pharmacogenomic study of gemcitabine efficacy in patients with metastatic pancreatic cancer: A multicenter, prospective, observational cohort study (GENESECT study).

Genetic polymorphisms of molecules are known to cause individual differences in the therapeutic efficacy of anticancer drugs. However, to date, germline mutations (but not somatic mutations) for anticancer drugs have not been adequately studied. The objective of this study was to investigate the association between germline polymorphisms of gemcitabine metabolic and transporter genes with carbohydrate antigen 19-9 (CA 19-9) response (decrease ≥50% from the pretreatment level at 8 weeks) and overall survival (OS) in patients with metastatic pancreatic cancer who receive gemcitabine-based chemotherapy. This multicenter, prospective, observational study enrolled patients with metastatic pancreatic cancer patients who were receiving gemcitabine monotherapy or gemcitabine plus nanoparticle albumin-bound paclitaxel combination chemotherapy. Thirteen polymorphisms that may be involved in gemcitabine responsiveness were genotyped, and univariate and multivariate logistic regression analyses were used to determine the association of these genotypes with CA 19-9 response and OS. The significance level was set at 5%. In total, 180 patients from 11 hospitals in Japan were registered, and 159 patients whose CA 19-9 response could be assessed were included in the final analysis. Patients who had a CA 19-9 response had significantly longer OS (372 vs. 241 days; p=.007). RRM1 2464A>G and RRM2 175T>G polymorphisms suggested a weak association with CA 19-9 response and OS, but it was not statistically significant. COX-2 -765G>C polymorphism did not significantly correlate with CA 19-9 response but was significantly associated with OS (hazard ratio, 2.031; p=.019). Genetic polymorphisms from the pharmacokinetics of gemcitabine did not indicate a significant association with efficacy, but COX-2 polymorphisms involved in tumor cell proliferation might affect OS.

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.

Impact of Cyclooxygenase-2 Polymorphism -765G>C (rs20417) on the Development of Ulcerative Colitis

Impact of Cyclooxygenase-2 Polymorphism -765G>C (rs20417) on the Development of Ulcerative Colitis

NF-қB and COX-2 Relation Between Endometrial Cancer and the Clinicopathological Parameters

Objective: Our study examines nuclear factor kappa B (NF-қB) and cyclooxygenase-2 (COX-2) polymorphisms in the most common gynecological cancer type, endometrial cancer, and the relationship between disease parameters and these polymorphisms.
 Methods: In our patient group; while 109 endometrial cancer patients were examined and treated in the Department of Gynecology and Obstetrics, Istanbul Medical Faculty, and 106 healthy women without the disease were included in the control group. DNA of blood samples taken from all groups were isolated; COX-2 765C> G and COX-2 1195A> G polymorphisms were studied with NF-қB-94 ins / delATTG. Genotypes analyzed using the PCR-based restriction fragment length polymorphisms (RFLP) method were investigated in terms of the relationship between endometrial cancer susceptibility and endometrial cancer disease parameters. Results in SPSS 17 program; Student’s t-tests were analyzed 
 using Anova, Fisher’s exact, and Chi-square tests.
 Results: NF-қB D + and DD genotype, COX-2 765 G + and GG genotype, and COX-2 1195 AA genotype were found to be significantly more common in the endometrial cancer group compared to the control group (p

309 Interleukin-1β, Cyclooxygenase-2 and Prostaglandin E2 Receptor 4 Genetic Polymorphisms May Modulate Inflammation Influencing the Severity of Psoriasis

This study aims to understand the relationship between the genetic polymorphisms of IL-1β, COX2 and EP4 and the biochemical parameters of the complete blood count in patients with psoriasis. 63 psoriasis patients were analysed and divided based on PASI: <5 (G1) and ≥5 (G2). Determination of IL-1β (rs16944; A>G), COX-2 (rs20417; G>C) and EP4 (rs4613763; T>C) was performed by endpoint genotyping. A statistically significant value of p<0.05 was considered. Allele A of IL-1β polymorphisms showed a 4.23-fold risk [1.22-14.59] for G2.

Single Nucleotide Polymorphisms in COX2 Is Associated with Persistent Primary Tooth and Delayed Permanent Tooth Eruption.

Persistent primary tooth (PPT) is a prevalent clinical condition that occurs when a primary tooth is over-retained beyond the established period of its normal exfoliation time, remaining in the oral cavity. Many factors could be involved in the risk of PPT; therefore, the aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) in the COX2 gene are associated with PPT. Children undergoing orthodontic treatment were screened. Orthopantomographs were assessed to evaluate PPT according to the Nolla stage of its permanent successor. The primary tooth was considered retained when its successor permanent tooth was in Nolla stage 8 and below the alveolar crypt, Nolla stage 9, or Nolla stage 10. A saliva sample from each child was collected and used for DNA extraction. A real-time PCR of two SNPs, rs689466 (−1195 G/A) and rs5275 (+665 T/C), was performed. A chi-square test was used to compare the allele and genotype distribution. Haplotype analysis was also performed. A total of 100 children were included in the study. Fifty-one had at least one PPT, while 49 children were classified as a control. The number of teeth persistent in the oral cavity ranged from 1 to 8. The genotype distribution was associated with PPT in the co-dominant model (p = 0.006) for SNP rs5275. The individuals that carry two T alleles (TT) compared with the individuals that carry at least one C allele (C + TC) had an almost three times higher chance of presenting with PPT (p = 0.012; OR = 2.99, CI95% 1.28 to 6.95–recessive model). The haplotype C-A for the SNPs rs5275 and rs689466, respectively, was significantly associated (p = 0.042). In conclusion, single nucleotide polymorphisms in the gene encoding for COX2 are associated with persistent primary tooth and may delay permanent tooth eruption.

Prostaglandin Synthase 2/Cyclooxygenase 2 Gene Polymorphisms and Susceptibility to Urothelial Bladder Cancer in an Iranian Population

Background: Prostaglandin-endoperoxide synthase 2, recognized as cyclooxygenase 2 (COX-2), is an important enzyme contributing to the generation of proinflammatory prostaglandins. It can play a role in increased tumor angiogenesis, apoptosis inhibition, metastasis, and invasion of tumors. Single nucleotide polymorphisms (SNPs) of the COX-2 promoter may associate with the cancer predisposition. In the present work, we aimed to explore whether SNPs of COX-2 gene affect both the risk of development and grade of bladder cancer. Method: This case-control study was performed and the genetic polymorphisms of six COX-2 SNPs including, intron 1 (rs2745557), intron 5 (rs16825748), intron 6 (rs2066826), T+8473C (rs5275), G-765 (rs20417), and A-1195G (rs68946) were genotyped in 80 healthy controls and 80 bladder cancer patients using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). To select independent prognostic factors, the univariate and multivariate analyses were implemented. Results: Univariate logistic regression model indicated a significant association between COX-2 765G>C heterozygous GC genotype and greater risk of bladder cancer (OR: 2.07; 95% CI: 1.03 - 4.15; P= 0.04). However, the multivariate logistic regression analysis showed no associations between COX-2 variants and bladder cancer development. Conclusion: We concluded that COX-2 polymorphisms do not contribute to the genetic susceptibility to urothelial bladder cancer in an Iranian population. However, the only genotype in which the frequency of alleles significantly differed between the two groups of high-grade tumors and low-grade tumors was COX -2 8473T> C (rs5275). Moreover, our findings showed that both smoking and family history of cancer play a role in susceptibility to bladder cancer.

Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.

TPS12135 Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p &lt; 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.

Connection of COX-2 variants to ankylosing spondylitis susceptibility.

This study aimed to explore the associations of COX-2 polymorphisms rs5275, rs20417, and rs2745557 with the susceptibility to ankylosing spondylitis among Chinese Han people. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) was adopted for genotyping COX-2 polymorphisms rs5275, rs20417, and rs2745557 among 109 AS patients and 122 healthy controls. Genotype distribution in the control group was examined for these three polymorphisms to test whether it conformed to Hardy-Weinberg equilibrium (HWE) expectation. A χ2 -test was employed to compare genotype and allele frequencies between the two groups. Besides this, logistic regression analyses were also performed to adjust age and gender. Apless than .05 represented a significant level. Genotype distribution of our studied polymorphisms showed fine conformity to HWE in the controls. An increasing effect on AS risk was detected for the polymorphism rs5275 under GG versus AA contrast (crude: OR,3.040; 95% CI,1.015-9.104), and the adjustment for age and gender did not change such a relationship (adjusted OR,3.307; 95% CI,1.065-10.268). After adjusting age and gender, both polymorphisms of rs20417 and rs2745557 demonstrated a negative relationship with the disease susceptibility. The GC genotype and C allele of rs20417 reduced the disease risk to 0.248 (adjusted: 95% CI,0.089-0.692) and 0.269 (95% CI,0.098-0.733), respectively, while the AA genotype and A allele of the latter to 0.413 (adjusted: 95% CI,0.191-0.893) and 0.676 (adjusted: 95% CI,0.466-0.981), respectively. Among Chinese Han people, COX-2 polymorphism rs5275 may contribute to increased risk of developing AS, while the polymorphisms rs20417 and rs2745557 may offer protection against disease incidence.

A Meta-Analysis for Association of Cyclooxygenase-2 Polymorphisms with Susceptibility to Prostate Cancer

A Meta-Analysis for Association of Cyclooxygenase-2 Polymorphisms with Susceptibility to Prostate Cancer

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&lt;0.0001; OR= 1.7, 95%CI= 1.249-2.331, p=0.0008; OR= 2.2, 95%CI= 1.61-3.014, p&lt;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.

Association of the cyclooxygenase-2 1759A allele with migraine in Chinese Han individuals.

Cyclooxygenase-2 (COX-2) is known to be involved in the pathogenesis of migraine, and some polymorphisms are known to affect the expression of COX-2. This retrospective case-control study aimed to explore the associations between the -765 G>C (rs20417), -1759 G>A (rs3218625), and -8473 C>T (rs5275) COX-2 polymorphisms and migraine in Chinese Han individuals. One hundred and ten unrelated Han Chinese patients with migraine and 108 healthy controls were recruited between 03/2014 and 08/2016 at the First Affiliated Hospital of Nanjing Medical University and the First People's Hospital of Lianyungang City. The genotypes of all polymorphisms in controls followed the Hardy-Weinberg equilibrium (P = 0.215, P = 0.884, and P = 0.689). There were differences in the genotype and allele distributions of the COX-2-1759G>A (Gly587Arg) polymorphism between the migraine and control groups (P = 0.038 and P = 0.040, respectively). Compared with the COX-2-1759AG genotype, GG genotype carriers had an increased risk of migraine (odds ratio (OR) = 8.720, 95% confidence interval (CI): 1.072–70.960, P = 0.038). The frequency of the COX-2-1759A allele in patients with migraine was significantly lower than the controls (OR = 0.119, 95%CI: 0.015–0.957, P = 0.040). Adjusted age and sex, a statistical difference was found in the dominant model of COX-2-1759 G>A (OR = 0.118, 95% CI 0.014 to 0.962, P = 0.046). No significant difference was detected regarding the -765G>C and -8473T>C polymorphisms between the two groups. The COX-2 1759A allele might be involved in the development of migraine in Chinese Han individuals, but this will have to be confirmed in large-scale studies.

Association between COX-2 and 15-PGDH polymorphisms and SLE susceptibility.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Prostaglandins E2 (PGE2), the product of the cyclo-oxygenase 2 (COX-2) enzyme, has critical roles in the etiology of autoimmune diseases. PGE2 level is controlled by a balance between its synthesis mediator (COX-2 enzyme) and its catabolic key enzyme (15-hydroxyprostaglandin dehydrogenase [15-PGDH] enzyme). In the present study, the associations of genotypic polymorphisms in COX-2 and 15-PGDH with SLE were investigated. One hundred and sixty SLE patients and 160 healthy controls participated in the study. The polymerase chain reaction - restriction fragments length polymorphism method was used for genotyping. The COX-2 rs2745557 G/A and 15-PGDH rs8752 G/A polymorphisms were investigated. Regarding the COX-2 rs2745557 single nucleotide polymorphism, there was no significant association between COX-2 rs2745557 polymorphism and SLE. However, the dominant models showed a marginally significant relation (P=.048, odds ratio=0.63, 95% CI=0.4-1.0). Regarding GA genotype of 15-PGDH rd8752 polymorphism, there was a significant difference between two groups with a 4.5-fold increase in SLE development (P=.0001). The frequency of the A allele was higher in SLE patients than that in controls, showing a 1.4-fold increase in SLE development (P=.018). All results showed the protective effects of the dominant model of COX-2 rs2745557 polymorphism and risk factor of 15-PGDH rs8752 polymorphism on SLE development.

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.

Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement.

Genetic polymorphisms could be involved in the individual rate of OTM (orthodontic tooth movement) corresponding to the clinical phenomenon of "slow movers" and "fast movers". This study evaluated, if genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6 are associated with the expression of RANKL, OPG, COX2 and IL6 by human periodontal ligament (hPDL) fibroblasts during OTM. Primary hPDL fibroblasts from periodontal connective tissue of teeth extracted from 57 human subjects for medical reasons were collected, isolated, cultivated and characterized. To simulate orthodontic forces in PDL pressure areas, a physiological compressive force of 2 g/cm2 was applied to the hPDL fibroblasts under cell culture conditions at 70% confluency for 48h, using a glass disc. Thereafter we analysed relative expression of RANKL, OPG, COX2 and IL6 by RT-qPCR. We also performed genotyping analysis of seven genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6. Relative gene expression was compared among the genotypes. The genotype TT in polymorphism rs9594738 (RANKL) had a higher RANKL expression in the recessive model (p = 0.021; TT vs. CT + CC). For polymorphism rs9594738 (RANKL), in the recessive model, TT was associated with a higher RANKL/OPG expression ratio (p = 0.013; TT vs. CT + CC). In the dominant model, GG genotype in rs5275 (COX2) was associated with a lower gene expression of COX2 (p = 0.04; GG vs. AA + AG). Genetic polymorphisms in genes associated with OTM affect the relative force-induced upregulation of these genes in hPDL fibroblasts.

The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran

Background: Esophageal cancer is recognized as one of the most fatal diseases around the world. Many factors are involved in the development of esophageal cancer, including genetic factors and inflammation. Cyclooxygenase-2 (COX-2) and its downstream signaling are the most important proinflammatory factors contributing to cancer. The present study aimed to evaluate the relationship between the polymorphisms and expression of COX-2 and prostaglandin-E2 (PGE2) level in patients with esophageal squamous cell carcinoma (ESCC) in Golestan Province (Iran), situated on the &amp;ldquo;esophageal cancer belt&amp;rdquo;.&#x0D; &#x0D; Methods: In this case-control study, blood and biopsy samples were obtained from ESCC patients and healthy controls. The COX-2 polymorphisms for -1195, -1290, -765, and +8473 SNPs were assayed using PCR-RFLP assay, while the level of PGE2 was measured using an ELISA kit. In addition, real-time PCR assay and immunohistochemistry (IHC) were performed to assay mRNA and protein expression of COX-2, respectively.&#x0D; &#x0D; Results: An association was found between 8473TC genotype and risk of ESCC (OR= 5.417, P= 0.036). In addition, mRNA and protein expression of COX-2 in ESCC patients was higher than the controls (P=0.001 and P=0.048, respectively). Based on the findings, the level of PGE-2 was significantly higher in ESCC patients, compared to the controls (P= 0.045). However, ROC curve analysis revealed PGE2 is a weak biomarker for diagnosis of ESCC. There was a significant relationship between the level of PGE2 and 8473CC, 8473TC, -765CC, and -1290AA genotypes (P= 0.028, P= 0.022, P= 0.024, and P= 0.011, respectively).&#x0D; &#x0D; Conclusion: Based on our results, functional polymorphisms of COX-2 (8473CC, 8473TC, - 765CC, and -1290AA) increase PGE2 level and carriers of these polymorphisms might be more susceptible to ESCC.

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.

Association of COX2 -765G>C promoter polymorphism and coronary artery disease in Korean population.

Cyclooxygenase-2 (COX2) plays a role in the formation of prostaglandins, which contribute to the inflammation involved in atherosclerosis. However, the role of the COX2 -765G>C polymorphism in susceptibility to coronary artery disease (CAD) is controversial. To identify the association between COX2 -765G>C polymorphism with CAD risk in Korean patients. We recruited 622 patients who were diagnosed to have coronary artery disease and 202 controls who did not have history and vascular disease risk factors. Using polymerase chain reaction-restriction fragment length polymorphism, the COX2 -765G>C polymorphism was analyzed in 622 Korean patients who received percutaneous coronary intervention and in 202 healthy control subjects. The GC+CC genotype frequencies of the -765G>C polymorphism were significantly different between the CAD and control groups. The COX2 -765G>C polymorphism showed peculiar associations with CAD according to the presence of hyperlipidemia and plasma folate levels. However, there were no associations between the -765G>C polymorphism and the rates of hypertension, diabetes mellitus, or homocysteine levels. This study suggests that the COX2 -765G>C polymorphism is a possible genetic determinant for the risk of CAD, and an individual risk factor in Koreans. Thus, further association studies between the COX2 polymorphism and atherosclerotic-related diseases such as cerebrovascular or cardiovascular diseases in other races or ethnicities will be needed.

Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility: Evidence from15 case-control studies.

Objective:Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups.Methods:We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association.Results:15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR = 1.67, 95%CI = 1.19–2.35, P = .003), heterozygous (GG vs CG: OR = 1.44, 95%CI = 1.03–2.02, P = .034), dominant (GC+CC vs GG: OR = 1.66, 95%CI = 1.18–2.34, P = .004), homozygous (GG vs CC:OR = 2.20, 95%CI = 1.07–4.54, P = .033), and recessive models (CC vs GG+CG:OR = 2.05, 95%CI = 1.09–3.85, P = .025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR = 2.22, 95%CI = 1.66–2.96, P < .001; GG vs CC: OR = 4.29, 95%CI = 1.94–9.50, P < .001; GG vs CG: OR = 1.86, 95%CI = 1.34–2.58, P < .001; CC vs GG+CG: OR = 3.73, 95%CI = 1.92–7.24, P < .001; GC+CC vs GG: OR = 2.20, 95%CI = 1.65–2.93, P < .001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR = 3.09, 95%CI = 1.80–5.32, P < .001).Conclusion:This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.

Roles of Cyclooxygenase-2 gene −765G > C (rs20417) and −1195G > A (rs689466) polymorphisms in gastric cancer: A systematic review and meta-analysis

BackgroundThe roles of cyclooxygenase-2 (COX2) −765G > C (rs20417) and −1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk. MethodsEligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method. ResultsThe COX2 gene −765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95–2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the −765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 −1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15–12.43 and OR = 2.48, 95% CI: 1.38–4.48, respectively), but not in −1195 A allele (OR = 1.96, 95% CI: 0.62–6.21, and OR = 1.24, 95% CI: 0.93–1.64, respectively). ConclusionsCOX2 −765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 −1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The −765G > C, rather than −1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.