FP受体基因多态性及其与拉坦前列腺素药物反应的关系
发布时间：2019-03-02 12:45
【摘要】：目的 探讨汉族POAG (primary open angle glaucoma,原发性开角型青光眼)和OHT (ocular hypertension,高眼压症)患者FP受体(Prostaglandin F2a Receptor,前列腺素F2α受体,又名FP受体)基因多态性及其与拉坦前列腺素药物反应的关系。方法 1、筛选汉族POAG和OHT患者后,提取外周血标本,并对入选患者的入选眼进行单一拉坦前列腺素药物治疗,用药后对病人进行随访,并记录眼压值及副作用等。 2、采用多聚酶链反应-限制性片段长度多态性(Polymerase Chain Reaction-restriction fragment length Polymorphism, PCR-RFLP)技术对FP受体基因rs3753380和rs3766355片段的多态性进行测定。结果 1、POAG和OHT患者FP受体的两个单核苷酸多态性(single nucleotide polymorphism, SNP)位点在基因型分布上,rs3753380的C/T等位基因和rs3766355的A/C等位基因分布的差异均无统计学意义(P0.05)。 2、rs3753380的CC与CT+TT基因型的比较中,两组除在入选眼别的差异有统计学意义外(P=0.006),其余在年龄、性别、诊断、入选眼CCT、入选眼视力、入选眼MD值、入选眼屈光度和入选眼0天眼压等方面的差异均无统计学意义(P0.05)。 3、rs3766355的AA与AC+CC基因型的比较中,两组除在入选眼MD值的差异有统计学意义外(P=0.03),其余在年龄、性别、诊断、入选眼CCT、入选眼视力、入选眼别,入选眼屈光度和入选眼0天眼压等方面的差异均无统计学意义(P0.05)。在CC与AA+AC基因型的比较中,两组除在入选眼CCT值的差异有统计学意义外(P=0.031),其余在年龄、性别、诊断、入选眼MD值、入选眼视力、入选眼别,入选眼屈光度和入选眼0天眼压等方面的差异均无统计学意义(P0.05)。 4、用药1周时,启动子位点rs3753380和内含子位点rs3766355的各基因型在各药物反应型分布的差异无统计学意义(P0.05)。 5、用药1月时,拉坦前列腺素高反应型与其他反应型相比,差异有统计学意义(rs3753380,TT:CC+CT[P=0.014, OR=0.80])。结论 1、首次进行了FP受体基因启动子位点rs3753380和内含子位点rs3766355在中国汉族POAG和OHT患者中发生率的研究。 2、rs3753380和rs3766355的SNP在中国汉族POAG和OHT患者中的分布符合Hardy-Weinberg遗传平衡规律,在小样本的研究中尚不能认为两SNP位点在汉族POAG和OHT患者的等位基因分布上有差异。 3、rs3753380的TT型突变纯合子比非突变纯合子对拉坦前列腺素的反应性可能更高。 4、本研究未发现rs3766355的SNP与拉坦前列腺素的药效之间的相关性。
[Abstract]:Objective to investigate the FP receptor (Prostaglandin F2a Receptor, prostaglandin F2 伪 receptor) in patients with primary open angle glaucoma (POAG (primary open angle glaucoma,) and OHT (ocular hypertension, ocular hypertension (IOP) in Han nationality. FP receptor) gene polymorphism and its relationship with drug response to latan prostaglandin. Methods 1. After screening the patients with POAG and OHT of Han nationality, the peripheral blood samples were extracted, and the selected eyes were treated with a single Ratan prostaglandin drug. The patients were followed up after the treatment, and the IOP and side effects were recorded. 2Polymerase chain reaction-restriction fragment length polymorphism (Polymerase Chain Reaction-restriction fragment length Polymorphism, PCR-RFLP) technique was used to detect the polymorphism of rs3753380 and rs3766355 fragments of FP receptor gene. Results 1. Two single nucleotide polymorphism (single nucleotide polymorphism, SNP) loci of FP receptor in Poag and OHT patients were genotypic distribution. There was no significant difference in the distribution of C / T allele of rs3753380 and A / C allele of rs3766355 (P0.05). 2. In the comparison of CC and CT TT genotypes in rs3753380, except for the difference between the two groups (P < 0.006), the others were in age, sex, diagnosis, CCT, visual acuity, and MD value in the selected eyes, but there was a significant difference between the two groups in the selected eyes (P < 0.05), but not in the other two groups (P < 0.05). There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). (3) in the comparison of AA and AC CC genotypes between Rs3766355 and Rs3766355, except for the difference of MD value in selected eyes (P < 0. 03), the others were in age, sex, diagnosis, CCT, visual acuity, and eye difference, and the other two groups had no significant difference in MD value (P < 0. 03). There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). In the comparison of CC and AA AC genotypes, except for the difference of CCT value in selected eyes (P < 0. 031), the others were in age, sex, diagnosis, MDvalue, visual acuity and eye type, and the other two groups had significant difference in CCT value (P < 0. 031), age, sex, diagnosis, MD value, visual acuity and eye type. There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). 4. At one week after treatment, there was no significant difference in the distribution of promoter site rs3753380 and intron site rs3766355 genotypes among drug response types (P0.05). 5. There was a significant difference between the Ratan-prostaglandin hyperreactive type and other reactive types at 1 month after administration (rs3753380,TT:CC CT [P0. 014, OR=0.80]). Conclusion 1. The incidence of FP receptor gene promoter site rs3753380 and intron rs3766355 in POAG and OHT patients of Chinese Han nationality was studied for the first time. 2. The distribution of rs3753380 and rs3766355 SNP in POAG and OHT patients of Han nationality was in accordance with the law of Hardy-Weinberg genetic balance. In the study of small samples, it could not be considered that the two SNP loci were different in the distribution of alleles between POAG and OHT patients of Han nationality. 3The TT type mutant homozygotes of rs3753380 may be more responsive to latan prostaglandins than non-mutant homozygotes. 4. No correlation was found between the SNP of rs3766355 and the efficacy of latan prostaglandins.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R775
本文编号：2433061
[Abstract]:Objective to investigate the FP receptor (Prostaglandin F2a Receptor, prostaglandin F2 伪 receptor) in patients with primary open angle glaucoma (POAG (primary open angle glaucoma,) and OHT (ocular hypertension, ocular hypertension (IOP) in Han nationality. FP receptor) gene polymorphism and its relationship with drug response to latan prostaglandin. Methods 1. After screening the patients with POAG and OHT of Han nationality, the peripheral blood samples were extracted, and the selected eyes were treated with a single Ratan prostaglandin drug. The patients were followed up after the treatment, and the IOP and side effects were recorded. 2Polymerase chain reaction-restriction fragment length polymorphism (Polymerase Chain Reaction-restriction fragment length Polymorphism, PCR-RFLP) technique was used to detect the polymorphism of rs3753380 and rs3766355 fragments of FP receptor gene. Results 1. Two single nucleotide polymorphism (single nucleotide polymorphism, SNP) loci of FP receptor in Poag and OHT patients were genotypic distribution. There was no significant difference in the distribution of C / T allele of rs3753380 and A / C allele of rs3766355 (P0.05). 2. In the comparison of CC and CT TT genotypes in rs3753380, except for the difference between the two groups (P < 0.006), the others were in age, sex, diagnosis, CCT, visual acuity, and MD value in the selected eyes, but there was a significant difference between the two groups in the selected eyes (P < 0.05), but not in the other two groups (P < 0.05). There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). (3) in the comparison of AA and AC CC genotypes between Rs3766355 and Rs3766355, except for the difference of MD value in selected eyes (P < 0. 03), the others were in age, sex, diagnosis, CCT, visual acuity, and eye difference, and the other two groups had no significant difference in MD value (P < 0. 03). There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). In the comparison of CC and AA AC genotypes, except for the difference of CCT value in selected eyes (P < 0. 031), the others were in age, sex, diagnosis, MDvalue, visual acuity and eye type, and the other two groups had significant difference in CCT value (P < 0. 031), age, sex, diagnosis, MD value, visual acuity and eye type. There was no significant difference in diopter and 0-day IOP between the selected eyes and the 0-day-old eyes (P0.05). 4. At one week after treatment, there was no significant difference in the distribution of promoter site rs3753380 and intron site rs3766355 genotypes among drug response types (P0.05). 5. There was a significant difference between the Ratan-prostaglandin hyperreactive type and other reactive types at 1 month after administration (rs3753380,TT:CC CT [P0. 014, OR=0.80]). Conclusion 1. The incidence of FP receptor gene promoter site rs3753380 and intron rs3766355 in POAG and OHT patients of Chinese Han nationality was studied for the first time. 2. The distribution of rs3753380 and rs3766355 SNP in POAG and OHT patients of Han nationality was in accordance with the law of Hardy-Weinberg genetic balance. In the study of small samples, it could not be considered that the two SNP loci were different in the distribution of alleles between POAG and OHT patients of Han nationality. 3The TT type mutant homozygotes of rs3753380 may be more responsive to latan prostaglandins than non-mutant homozygotes. 4. No correlation was found between the SNP of rs3766355 and the efficacy of latan prostaglandins.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R775
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