Analysis of association between genetic polymorphisms of the prostaglandin F2 IA receptor gene and response to latanoprost.

拉坦前列素是一种前列腺素f2O类似物，广泛用于降低青光眼患者的眼压(10P)，尽管在某些情况下反应出乎意料地弱。目前尚不清楚是什么原因导致不同患者对拉坦前列素的弱反应。为探讨前列腺素F2n受体(FP受体)基因多态性与拉坦前列素治疗效果的关系，对FP受体基因进行单核苷酸多态性(SNPs)分析，并通过DNA直接测序确定基因分型。在本研究中发现了10个SNP。在3个时间点测量100例正常人双眼的基线眼压。拉坦前列素(0.005%)用于单眼，每日1次，连用7天。在第7天再次测量昼夜10P。通过治疗眼10P减少百分比减去非治疗眼10P波动来评估对拉坦前列素的反应。一个SNP，rs375…My 3380位于FP受体基因启动子区域，与日均10p下降百分率显著相关(CC，20.3±1.5%；CT+TT，15.6±1.2%，P=0.0316)。AIOP与其他SNPs无相关性。我们根据%ΔIOP将受试者分为三组：低响应者(%ΔIOP；10%)、中等响应者(10%ΔIOP&lt；25%)和高响应者(%Δ10p&lt；25%)。当分析按%oIOP分类的类别时，不仅rs3753380，而且rs3766355，内含子1中的SNP，都与拉坦前列素的疗效相关。报告荧光素酶基因的启动子分析显示，rs3766355的C等位基因和rs3753380的T等位基因存在于FP受体基因转录活性较低的结构中。在正常志愿者中，FP受体基因启动子和内含子1区域的rs3753380和rs3766355 SNPs与短期拉坦前列素治疗的疗效相关。这些SNPs的基因型别可能是拉坦前列素疗效变异的重要决定因素。较少

Latanoprost, a prostaglandin F2o analogue, is widely used to lower the intraocular pressure (10P) in patients with glaucoma although in some cases the response is unexpectedly weak. It is currently unknown what is responsible for the weak responses to latanoprost in different patients. We attempted to evaluate the relationship between polymorphisms of the prostaglandin F2n receptor (FP receptor) gene and the effectiveness of topical latanoprost treatment in normal volunteers.Single nucleotide polymorphisms (SNPs) in the FP receptor gene were searched and the genotype was determined mainly by direct DNA sequencing. Ten SNPs were identified in this study. Baseline IOPs of both eyes of 100 normal subjects were measured at three time points. Latanoprost (0.005%) was applied to one eye once daily, for 7 days. Diurnal 10P was measured again on day 7. Response to latanoprost was evaluated by percent 10P reduction in the treated eye minus 10P fluctuations of the non-treated eye. One SNP, rs375 … More 3380, was located in the promoter region of the FP receptor gene and was significantly correlated with the mean diurnal percent 10P reduction (%AIOP) (CC, 20.3 ± 1.5% (mean ± SEM); CT + TT, 15.6 ± 1.2%, P = 0.0316). The %AIOP was not correlated with other SNPs. We classified subjects by the %ΔI0P into 3 groups: low-responders (%ΔIOP <10%), medium-responders (10%<%ΔIOP <25%), and high-responders (%Δ10P<25%). When the category classified by the %oIOP was analyzed, not only rs3753380 but also rs3766355, a SNP in intron 1, were associated with the degree of response to latanoprost. A promoter assay with a reporter luciferase gene revealed that the C allele of rs3766355 and T allele of rs3753380 were found in constructs with lower transcriptional activity of the FP receptor gene.rs3753380 and rs3766355, SNPs in the promoter and intron 1 regions of the FP receptor gene, correlate with a response to short-term latanoprost treatment in normal volunteers. The genotype of these SNPs may be an important determinant of variability in response to latanoprost. Less