Single Nucleotide Polymorphisms In PTGS2 Research Articles

The -1195A>G polymorphism in Ciclooxygenase-2 gene is associated with lower risk of endometriosis

ObjectivesThis study aimed to evaluate the potential role of the PTGS2 single nucleotide polymorphisms (SNPs) -1195 A>G and +8473 T>C in endometriosis’ development, and characterizing their association with the prognostic features of the disease. Study DesignDNA from 254 women with endometriosis and 267 controls, recruited from two reference hospitals from the Brazilian public health system, were genotyped using TaqMan allelic discrimination assays. The association between SNPs and endometriosis features was evaluated by multivariate logistic regression, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). Results and ConclusionThere were significant differences between cases and controls regarding age (P < 0.001), body mass index (BMI) (P = 0.001), educational level (P < 0.001), physical activity (P = 0.003), smoking status (P < 0.001), contraception use (P = 0.02), family history of endometriosis (P = 0.002) and all symptoms (P < 0.001). The distribution of -1195 A > G was statistically different between the groups, suggesting a lower risk of developing the disease for the carriers of the −1195 GG genotype (OR = 0.19; 95% CI = 0.04 – 0.93). No differences were found for the +8473 T>C between the two groups and neither in prognostic features of the disease for both PTGS2 SNPs. In conclusion, PTGS2 -1195A>G SNP was negatively associated with development of endometriosis and the two groups were statistically different regarding age, BMI, educational level, physical activity, smoking status, contraception use, history of endometriosis and all endometriosis symptoms.

Association of a novel GABRG2 splicing variation and a PTGS2/COX-2 single nucleotide polymorphism with Taiwanese febrile seizures

Abstract: Febrile seizure (FS) is the most common type of convulsion in infants and young children. The occurrence of FS in a subset of children with febrile illness suggested genetic factors may have an important effect on the predisposition of the disease. Using targeted next generation sequencing (NGS), a novel splicing variation (NM_198903.2:c.1249-1G>T) was identified in the γ-aminobutyric acid type A (GABA-A) receptor γ2 subunit (GABRG2) gene of a FS patient. To investigate possible association of FS with single nucleotide polymorphisms (SNPs) in prostaglandin-endoperoxide synthase-2 (prostaglandin G/H synthase-2; PTGS2/cyclooxygenase-2; COX2) gene involving in thermoregulatory pathway, eight SNPs, rs689465, rs689466, rs20417, rs13306038, rs201931599, rs689470, rs4648306 and rs4648308, along with 2 previously reported variations in IL1RN (86-bp VNTR) and IL10 (rs1900872) were genotyped and utilized for case-control association studies on 35 FS and 31 non-FS controls. A single SNP (rs689466) localized at 5′-1192 of the PTGS2 gene exhibited significant association with FS (p=0.045) based on case-control allelic association analyses. A significant decrease in the frequency of the G allele in FS (0.357) was observed compared to that in controls (0.536) with an estimated odds ratio (OR) of 0.48 (95% CI, 0.23–0.99) for the G versus A allele. Using case-control genotypic association analysis, the −1192 A allele is most likely to confer susceptibility to FS by a recessive action model (p=0.045, pointwise empirical p value (EMP1)=0.049). The association of SNPs in PTGS2, in addition to IL6, IL-6 receptor (IL6R) and prostaglandin E receptor 3 (PTGER3) in prior reports, with FS suggests their possible action in concert to modulate phenotypes in FS as well as the involvement of thermoregulatory pathway in pathogenesis of FS.

SNPs in PTGS2 and LTA predict pain and quality of life in long term lung cancer survivors

PurposeLung cancer survivors report the lowest quality of life relative to other cancer survivors. Pain is one of the most devastating, persistent, and incapacitating symptoms for lung cancer survivors. Prevalence rates vary with 80–100% of survivors experiencing cancer pain and healthcare costs are five times higher in cancer survivors with uncontrolled pain. Cancer pain often has a considerable impact on quality of life among cancer patients and cancer survivors. Therefore, early identification, and treatment is important. Although recent studies have suggested a relationship between single nucleotide polymorphisms (SNPs) in several cytokine and inflammation genes with cancer prognosis, associations with cancer pain are not clear. Therefore, the primary aim of this study was to identify SNPs related to pain in lung cancer survivors. Patients and methodsParticipants were enrolled in the Mayo Clinic Lung Cancer Cohort upon diagnosis of their lung cancer. 1149 Caucasian lung cancer survivors (440 surviving <3 years; 354 surviving 3–5 years; and 355 surviving >5 years) completed study questionnaires and had blood DNA samples available. Ten SNPS from PTGS2 and LTA genes were selected based on the serum-based studies in the literature. Outcomes included pain, and quality of life as measured by the SF-8. ResultsOf the 10 SNPs evaluated in LTA and PTGS2 genes, 3 were associated with pain severity (rs5277; rs1799964), social function (rs5277) and mental health (rs5275). These results suggested both specificity and consistency of these inflammatory gene SNPs in predicting pain severity in lung cancer survivors. ConclusionThese results provide support for genetic predisposition to pain severity and may aid in identification of lung cancer survivors at high risk for morbidity and poor QOL.

LPS-mediated production of pro/anti-inflammatory cytokines and eicosanoids in whole blood samples: Biological effects of +896A/G TLR4 polymorphism in a Sicilian population of healthy subjects

Toll-like receptors (TLRs) are the principal mediators of rapid microbial recognition: the lipopolysaccharide (LPS) receptor TLR4 seems to have a paradigmatic role. Single nucleotide polymorphisms (SNPs) in the TLR4 gene, such as +896A/G, known to attenuate receptor signaling, have been described. The +896A/G SNP is significantly less frequent in patients with myocardial infarction, Alzheimer's disease or prostate cancer, whereas it is overrepresented in centenarians. To clarify and confirm the biological effects of +896A/G SNP and its role in the pathophysiology of age-related diseases and longevity, we assessed the levels of IL-6, TNF-α, IL-10 and eicosanoids (LTB4 and PGE2) in LPS-stimulated whole blood samples in vitro of 50 young healthy Sicilians, screened for the presence of this SNP. To evaluate the possible influence of SNPs in PTGS2 and 5-Lo genes on eicosanoid production, the enrolled individuals were also genotyped for −765G/C PTGS2 and −1708G/A 5-Lo SNPs. Both pro-inflammatory cytokines and eicosanoids were significantly lower in carriers bearing the TLR4 mutation, whereas the anti-inflammatory IL-10 values were higher. On the basis of data reported herein, some suggestions can be drawn. First, pathogen load, by interacting with the host genotype, determines the type and intensity of inflammatory responses, according to the pro-inflammatory status and tissue injury, implicated in the pathophysiology of major age-related diseases. Second, adequate control of inflammatory response might reduce the risk of these diseases, and, reciprocally, might increase the chance of extended survival in an environment with reduced antigen (that is, pathogen) load.

A New Cyclo-Oxygenase-2 Gene Variant in the Han Chinese Population is Associated with an Increased Risk of Gastric Carcinoma

Cyclo-oxygenase-2 (COX-2, also known as prostaglandin synthase 2) influences carcinogenesis through regulation of angiogenesis, apoptosis, and cytokine expression. COX-2 is encoded by the gene PTGS2. Several studies have suggested that PTGS2 single-nucleotide polymorphisms (SNPs) are involved in gastrointestinal carcinogenesis. In this study, we observed the PTGS2 Val511Ala (5939T/C) polymorphism in the Chinese population for the first time, and investigated whether this polymorphism might contribute to gastric cancer in a case-control study conducted in the Gansu province of China, a high-risk area for gastric cancer. We determined the genotypes of 110 gastric cancer patients and 138 controls using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis. Data were statistically analyzed using a chi-squared test and a logistic regression model. In our analysis, PTGS2 5939C allele carriers were at increased risk of gastric cancer (odds ratio [OR] 1.742; 95% confidence interval [CI] 1.009, 3.005; p = 0.045). We also found an interaction between Helicobacter pylori infection, a family history of gastric cancer, and presence of the 5939C allele. This study further indicated that H. pylori-positive status and family history jointly contribute to a higher risk of gastric cancer.