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

拉坦前列素，一种前列腺素F20类似物，被广泛用于降低青光眼患者的眼内压（10 P），尽管在某些情况下，反应出乎意料地弱。目前尚不清楚不同患者对拉坦前列素反应弱的原因。我们试图评估前列腺素F2 n受体（FP受体）基因多态性与拉坦前列素局部治疗的有效性之间的关系，搜索FP受体基因的单核苷酸多态性（SNP），主要通过直接DNA测序确定基因型。在这项研究中确定了10个SNP。在三个时间点测量100名正常人双眼的基线IOP。拉坦前列素（0.005%）每天一次应用于一只眼睛，持续7天。在第7天再次测量昼夜10 P。通过治疗眼的10 P减少百分比减去未治疗眼的10 P波动来评价对拉坦前列素的反应。一个SNP，rs375 ...更多信息 3380，位于FP受体基因的启动子区，与平均昼夜10 P降低百分比（%AIOP）显著相关（CC，20.3 ± 1.5%（mean ± SEM）; CT + TT，15.6 ± 1.2%，P = 0.0316）。%AIOP与其他SNPs不相关。我们根据%Δ I 0 P将受试者分为3组：低反应者（%ΔIOP <10%）、中反应者（10%<%ΔIOP <25%）和高反应者（%Δ 10 P <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）与拉坦前列素的反应程度相关。报告荧光素酶基因的启动子检测显示，C等位基因的rs3766355和T等位基因的rs3753380被发现在构建体的FP受体基因的转录活性较低。rs3753380和rs3766355，SNP的启动子和内含子1区的FP受体基因，与短期拉坦前列素治疗的反应在正常志愿者。这些SNP的基因型可能是拉坦前列素应答变异性的重要决定因素。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