Influence of PTGS1, PTGFR, and MRP4 genetic variants on intraocular pressure response to latanoprost in Chinese primary open-angle glaucoma patients.

PURPOSE: The purpose of this study is to evaluate the association between variants in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin F (2α) receptor (PTGFR), and multidrug resistance protein 4 (MRP4) genes and intraocular pressure (IOP) response to latanoprost in Chinese patients with primary open-angle glaucoma (POAG). METHODS: The IOP response to latanoprost was evaluated by percent IOP reduction (%ΔIOP) in the treated eye with the formula %ΔIOP = (Baseline IOP values - IOP values posttreatment) / Baseline IOP values × 100 %. Polymorphisms in PTGS1 (rs3842787 and rs10306114), PTGFR (rs3753380 and rs3766355), and MRP4 (rs11568658 and rs11568668) genes were detected by direct DNA sequencing. The differences among %ΔIOP of genotypes or haplotypes were obtained by use of the Mann-Whitney U test. Association analyses were performed by multiple linear regression analysis. RESULTS: Latanoprost were prescribed to 63 subjects, 60 of which met the inclusion/exclusion criteria for the current study. Notably, the %ΔIOP in the rs11568658 GT heterozygous genotype was 10.4 %ΔIOP lower than that of GG homozygous wild-type on day 7 (15.7 ± 2.52 vs. 26.1 ± 2.88, P=0.003), and the corresponding results in the rs10306114 AG heterozygous genotype and AT haplotype constructed by rs3753380 and rs3766355 on day 7 were 7.2 and 10.3 %ΔIOP (P<0.05). Interestingly, similar results were also observed on day 30 (P=0.008, P=0.006, and P=0.002, respectively). Multiple regression analysis showed that heterozygous genotypes of rs10306114, rs11568658, and carrier of AT haplotype were significantly correlated with the lower %ΔIOP. On day 30, the above variations explained 9.9, 10.7, and 17.7 % of the total variability of %ΔIOP in the Chinese POAG patients, respectively. CONCLUSION: rs10306114, rs3753380, rs3766355, and rs11568658 single-nucleotide polymorphisms (SNPs) correlate with a response to latanoprost treatment in patients with POAG. These SNPs may be important determinants of variability in response to latanoprost.

Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes from patients with acute myocardial infarction and modulates the early inflammatory response.

BACKGROUND: We examined the effect of atorvastatin on the expression of COX-2 in peripheral blood monocytes from patients with early stage of acute myocardial infarction (AMI), and the plasma C-reactive protein (CRP) concentrations were also examined. METHODS: Patients with AMI (n = 40) and with stable coronary heart disease (CHD; n = 18) were registered, and patients with AMI were randomly separated to a group that received routine therapy (group A, n = 20) or to a group that received routine therapy plus atorvastatin at 20 mg/day (group B, n = 20) for a week. Peripheral blood monocytes from patients with AMI both before and after treatment and from patients with stable CHD were isolated and cultured for 24 h. COX-2 mRNA expression was analyzed by reverse transcription-PCR. We measured concentrations of CRP in plasma by ELISA. RESULTS: COX-2 expression was activated in peripheral blood monocytes from patients with AMI [0.92 (0.13)] compared with patients with stable CHD [0.19 (0.08)]; after a week of treatment, COX-2 expression in group B (reduced by 66%) was obviously lower than in group A (reduced by 24%; P <0.05). Plasma concentrations of CRP from patients with AMI [43.3 (14.9) mg/L] were increased compared with those from patients with stable CHD [1.65 (0.78) mg/L; P <0.05]; after a week of treatment, CRP concentrations in group B (reduced by 62%) were lower than in group A (reduced by 35%; P <0.05). COX-2 expression in peripheral blood monocytes from patients with AMI was positively correlated with plasma CRP concentration (r = 0.662; P <0.05). CONCLUSIONS: COX-2 may promote acute inflammatory process after AMI. Atorvastatin may improve the antiinflammatory effects through the COX-2 pathway.

[Significance and expression of cyclooxygenase-2 mRNA in peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of cyclooxygenase-2 (COX-2) mRNA in peripheral blood monocytes in patients with acute coronary syndrome (ACS), and to explore the effect of the expression of COX-2 mRNA in ACS. METHODS: The expressions of COX-2 mRNA in peripheral blood monocytes from 18 normal subjects and 42 ACS patients were analyzed by reverse transcription polymerase chain reaction (RT-PCR), and the monocytes from patients were incubated with celecoxib in vitro. The concentrations of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in supernates of monocytes were measured by enzyme-linked immunosorbent assays (ELISA). RESULTS: The expression of COX-2 mRNA and the secrections of IL-6 and MMP-9 in peripheral blood monocytes in ACS patients significantly increased compared with those from normal controls [0.61 +/- 0.17 vs 0.11 +/- 0.09; (97.24 +/- 11.21) ng/L vs (22.15 +/- 6.30) ng/L; (41.20 +/- 8.41) g/L vs (11.76 +/- 4.23) g/L; all P < 0.05, respectively]. Celecoxib reduced IL-6 and MMP-9 secretion level of monocytes from ACS patients up to 48% and 50% respectively (all P < 0.05), in a concentration-dependent manner. CONCLUSION: COX-2 in peripheral blood monocytes may play an important role in the acute coronary syndrome.