FP受體基因多態(tài)性及其與拉坦前列腺素藥物反應(yīng)的關(guān)系
發(fā)布時(shí)間：2019-03-02 12:45
【摘要】：目的 探討漢族POAG (primary open angle glaucoma,原發(fā)性開角型青光眼)和OHT (ocular hypertension,高眼壓癥)患者FP受體(Prostaglandin F2a Receptor,前列腺素F2α受體,又名FP受體)基因多態(tài)性及其與拉坦前列腺素藥物反應(yīng)的關(guān)系。方法 1、篩選漢族POAG和OHT患者后,提取外周血標(biāo)本,并對(duì)入選患者的入選眼進(jìn)行單一拉坦前列腺素藥物治療,用藥后對(duì)病人進(jìn)行隨訪,并記錄眼壓值及副作用等。 2、采用多聚酶鏈反應(yīng)-限制性片段長(zhǎng)度多態(tài)性(Polymerase Chain Reaction-restriction fragment length Polymorphism, PCR-RFLP)技術(shù)對(duì)FP受體基因rs3753380和rs3766355片段的多態(tài)性進(jìn)行測(cè)定。結(jié)果 1、POAG和OHT患者FP受體的兩個(gè)單核苷酸多態(tài)性(single nucleotide polymorphism, SNP)位點(diǎn)在基因型分布上,rs3753380的C/T等位基因和rs3766355的A/C等位基因分布的差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 2、rs3753380的CC與CT+TT基因型的比較中,兩組除在入選眼別的差異有統(tǒng)計(jì)學(xué)意義外(P=0.006),其余在年齡、性別、診斷、入選眼CCT、入選眼視力、入選眼MD值、入選眼屈光度和入選眼0天眼壓等方面的差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 3、rs3766355的AA與AC+CC基因型的比較中,兩組除在入選眼MD值的差異有統(tǒng)計(jì)學(xué)意義外(P=0.03),其余在年齡、性別、診斷、入選眼CCT、入選眼視力、入選眼別,入選眼屈光度和入選眼0天眼壓等方面的差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。在CC與AA+AC基因型的比較中,兩組除在入選眼CCT值的差異有統(tǒng)計(jì)學(xué)意義外(P=0.031),其余在年齡、性別、診斷、入選眼MD值、入選眼視力、入選眼別,入選眼屈光度和入選眼0天眼壓等方面的差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 4、用藥1周時(shí),啟動(dòng)子位點(diǎn)rs3753380和內(nèi)含子位點(diǎn)rs3766355的各基因型在各藥物反應(yīng)型分布的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 5、用藥1月時(shí),拉坦前列腺素高反應(yīng)型與其他反應(yīng)型相比,差異有統(tǒng)計(jì)學(xué)意義(rs3753380,TT:CC+CT[P=0.014, OR=0.80])。結(jié)論 1、首次進(jìn)行了FP受體基因啟動(dòng)子位點(diǎn)rs3753380和內(nèi)含子位點(diǎn)rs3766355在中國(guó)漢族POAG和OHT患者中發(fā)生率的研究。 2、rs3753380和rs3766355的SNP在中國(guó)漢族POAG和OHT患者中的分布符合Hardy-Weinberg遺傳平衡規(guī)律,在小樣本的研究中尚不能認(rèn)為兩SNP位點(diǎn)在漢族POAG和OHT患者的等位基因分布上有差異。 3、rs3753380的TT型突變純合子比非突變純合子對(duì)拉坦前列腺素的反應(yīng)性可能更高。 4、本研究未發(fā)現(xiàn)rs3766355的SNP與拉坦前列腺素的藥效之間的相關(guān)性。
[Abstract]:Objective to investigate the FP receptor (Prostaglandin F2a Receptor, prostaglandin F2 偽 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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R775
本文編號(hào)：2433061
[Abstract]:Objective to investigate the FP receptor (Prostaglandin F2a Receptor, prostaglandin F2 偽 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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R775
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