rs20417

This functional study examined how PTGS2 gene variants in the promoter region and 3'-UTR modulate COX-2 gene expression using luciferase reporter assays in MCF-7 and HEK293FT cells. The rs689466 G variant showed consistent enhancing effects (~2-fold increase in transcriptional activity, P<0.001), while rs20417 C reduced activity by 40% in MCF-7 cells. The 3'-UTR rs5275 variant had variable effects depending on cell line, but the transcriptional effect of rs689466 remained detectable.

A prospective study of 568 Chinese non-small-cell lung cancer (NSCLC) patients found that four immune gene polymorphisms were independently associated with survival: IL-5R rs11713419 (5'-UTR, P=0.001), IL23R rs6682925 (5'-FR, P=0.017), TLR1 rs5743551 (5'-FR, P=0.02), and TLR3 rs3775291 (Leu412Phe, P=0.01). Patients carrying 1 unfavorable locus had 124% increased mortality risk (HR=2.24, 95% CI: 1.33-3.75), and those with 2-4 unfavorable loci had 175% increased risk (HR=2.75, 95% CI: 1.67-4.51). Combined SNP and clinical risk score model achieved 5-year AUC of 0.831 versus 0.484 for clinical factors alone.

This case-control association study identified rs10483032 in the CBR3 gene as associated with type 2 diabetes and insulin resistance in Chinese populations (combined OR = 1.29, 95% CI = 1.14-1.47, P < 0.0001). The association was replicated in multiple Chinese samples and validated in the FUSION GWAS. Functional studies demonstrated CBR3 expression increases during adipocyte differentiation, and CBR3 knockdown enhanced adipogenesis, suggesting the risk variant modulates type 2 diabetes susceptibility through effects on adipogenesis and insulin sensitivity.

This review examines COX-2 (PTGS2) genetic variants and their association with gastric cancer susceptibility. Key variants include rs689466 (OR=1.19, p=0.002), rs20417 (OR=1.26, p<0.001), rs3218625 (OR=1.62, p=0.039), and rs5275 (OR=1.14, p=0.030), which increase gastric cancer risk through enhanced transcriptional activity or mRNA stability. The paper synthesizes data from multiple case-control studies and the authors' own analyses in Chinese populations (296-660 cases each), establishing COX-2 polymorphisms as potential biomarkers for cancer risk stratification.

A case-control study analyzed the rs20417 76 G/C polymorphism in the COX2 gene among 46 patients with chronic polyposis rhinosinusitis (SRSwP), 39 with chronic rhinosinusitis (SRS), and 31 controls. No significant differences were found in allele frequencies (G: 83.7% SRSwP vs 88.7% controls, OR=0.7, 95% CI: 0.25-1.7) or genotype distributions between groups. A non-significant trend was observed toward increased G/G genotype frequency in SRSwP patients compared to controls.

This case-control study identified a novel COX-2 exon 10 SNP (1759G>A, rs3218625) that causes a Gly587Arg amino acid substitution. Functional assays demonstrated that COX-2-587Arg has significantly higher enzymatic activity toward arachidonic acid (13.8 vs 11.2 U/mg, P=0.012). In 1,026 esophageal squamous-cell carcinoma patients and 1,270 controls, individuals carrying the 1759A allele had increased ESCC risk (OR=1.91, 95% CI=1.39-2.62, P<0.0001), with heterozygotes showing an OR of 1.87 (95% CI=1.36-2.57).

A case-control study of 147 oral premalignant lesion (OPL) patients and 147 healthy controls found that the COX-2 exon10+837T>C variant (rs5275) was associated with significantly reduced OPL risk (OR=0.48, 95% CI 0.28-0.80, p=0.005). Common haplotype WMW (containing the rs5275 variant) and diplotype WWW/WMW both showed reduced OPL risk (ORs 0.55 and 0.44, respectively), with protective effects observed in males, younger subjects, ever smokers, and ever drinkers.

A case-control study in Brazilian women investigating the association between PTGS2 (COX-2) gene polymorphisms and breast cancer risk. The study identified nine SNPs in the promoter and 3'-UTR regions, with four frequent SNPs (rs689465, rs689466, rs20417, rs5275) selected for analysis. While rs5275 TC heterozygotes showed increased frequency in cases (OR=1.44, P=0.043), the authors concluded there was no strong association between the most frequent PTGS2 SNPs and breast cancer risk.

This association study identified five SNPs in the PTGS2 gene (cyclooxygenase-2) and tested their association with type 2 diabetes mellitus (T2DM) in approximately 1,000 Pima Indians. Two promoter/intronic variants were significantly associated with T2DM: rs20417 (OR=1.6 per C allele copy, P=0.01) and rs2066826 (OR=1.5 per T allele copy, P=0.01), with individuals carrying variant alleles showing 30% higher diabetes prevalence. The rs20417 C allele variant has been shown to reduce PTGS2 promoter activity, suggesting a biological mechanism through altered gene expression affecting insulin secretion.