本文關(guān)鍵詞：雄激素及糖皮質(zhì)激素代謝關(guān)鍵基因多態(tài)性與多囊卵巢綜合征遺傳易感性的關(guān)聯(lián)研究　出處：《南京醫(yī)科大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 多囊卵巢綜合征 HSD17B5 HSD17B6 基因多態(tài)性 高雄激素血癥 多囊卵巢綜合征 HSD11B1 H6PD 基因多態(tài)性 高雄激素血癥

【摘要】：[目的]高雄激素血癥是多囊卵巢綜合征(PCOS)諸多臨床表現(xiàn)中重要特征之一。17β羥基類固醇脫氫酶5型(HSD17B5)基因和17β羥基類固醇脫氫酶6型(HSD17B6)基因可以編碼特殊的酶類,參與雄激素的合成和代謝,因此是雄激素合成和代謝的關(guān)鍵基因。本研究評(píng)價(jià)HSD17B5和HSD17B6基因的多態(tài)性與多囊卵巢綜合征患者患病風(fēng)險(xiǎn)和臨床表現(xiàn)之間的關(guān)系。[方法]收集335名PCOS患者為研究對(duì)象,對(duì)照組為354名正常妊娠婦女,利用TaqMan等位基因分型(AD)技術(shù)對(duì)這兩組人群中HSD17B5 (rsl937845和rs12529)和HSD17B6 (rs898611)基因位點(diǎn)多態(tài)性進(jìn)行檢測(cè),比較其差異性。同時(shí)測(cè)定PCOS患者基礎(chǔ)狀態(tài)下生殖內(nèi)分泌、代謝指標(biāo),包括卵泡刺激素(FSH)、黃體生成素(LH)、雌二醇(E2)、睪酮(T)、泌乳素(PRL)、空腹血糖(Fasting glucose)、空腹胰島素(Fasting insulin)、硫酸脫氫表雄酮(DHEAS),利用Stata軟件進(jìn)行統(tǒng)計(jì)分析,對(duì)比PCOS組與對(duì)照組基因位點(diǎn)多態(tài)性之間的差異性,分析PCOS組臨床生化結(jié)果與各基因位點(diǎn)多態(tài)性之間的相關(guān)性。[結(jié)果]我們發(fā)現(xiàn)HSD17B5基因rs1937845位點(diǎn)各基因型分布在PCOS組和對(duì)照組中存在顯著性差異,該位點(diǎn)CT基因型和T等位基因在PCOS組分布顯著高于對(duì)照組(P=-0.002,P=-0.012),說(shuō)明HSD17B5基因rs1937845位點(diǎn)CT基因型和T等位基因是PCOS的易感基因。我們比較PCOS患者臨床內(nèi)分泌指標(biāo)與HSD17B5和HSD17B6各多態(tài)位點(diǎn)之間的關(guān)系,發(fā)現(xiàn)HSD17B5基因rs12529位點(diǎn)CC基因型血睪酮水平顯著高于GG基因型(P=-0.034)；該基因rs1937845位點(diǎn)TT基因型睪酮水平高于CC基因型(P=-0.053),且該位點(diǎn)TT基因型穩(wěn)態(tài)模型胰島素分泌指數(shù)(HOMA-B%)顯著高于CC基因型(P=-0.045)。將PCOS組按睪酮水平的高低分為高雄激素血癥組和非高雄激素血癥組,分析各SNP位點(diǎn)多態(tài)性與高雄激素血癥之間的關(guān)系,我們發(fā)現(xiàn)HSD17B5rs12529位點(diǎn)GC基因型(P=-0.054)和C等位基因(P=-0.002)及rs1937845位點(diǎn)CT基因型(P=-0.047)和T等位基因(P=-0.004)與高雄激素血癥均密切相關(guān)。未發(fā)現(xiàn)HSD17B6基因rs898611位點(diǎn)基因多態(tài)性與PCOS患病風(fēng)險(xiǎn)之間的相關(guān)性。[結(jié)論]本研究提示HSD17B5基因rs 1937845位點(diǎn)基因多態(tài)性與PCOS遺傳易感性相關(guān),該位點(diǎn)CT基因型與T等位基因可增加罹患PCOS的風(fēng)險(xiǎn)。HSD17B5可能參與了雄激素的代謝調(diào)節(jié),該基因rs12529位點(diǎn)GC基因型和C等位基因和rs1937845位點(diǎn)CT基因型和T等位基因增加了PCOS患者罹患高雄激素血癥的風(fēng)險(xiǎn)。未發(fā)現(xiàn)HSD17B6基因rs898611位點(diǎn)多態(tài)性與PCOS遺傳易感性之間的關(guān)聯(lián)性。[目的]PCOS患者常出現(xiàn)肥胖、糖耐量的異常(或糖尿病)及血清胰島素水平的升高,人體中葡萄糖的代謝、脂肪分布及脂質(zhì)代謝均有糖皮質(zhì)激素參與其中并起重要作用。11β羥基類固醇脫氫酶1型(HSD11B1)是調(diào)節(jié)糖皮質(zhì)激素活性的關(guān)鍵酶,主要表現(xiàn)為還原型煙酰胺腺嘌呤二核苷酸磷酸(NADPH)依賴型的還原酶活性,H6PD可以催化煙酰胺腺嘌呤二核苷酸(NAD)還原為NADPH,兩者協(xié)同作用影響糖皮質(zhì)激素的活性,因此HSD11B1與H6PD是糖、脂代謝的關(guān)鍵基因。本研究探討糖皮質(zhì)激素代謝關(guān)鍵基因HSD11B1和H6PD基因多態(tài)性與PCOS易感性的關(guān)系。[方法]本研究中PCOS組為335名PCOS患者,對(duì)照組為354名妊娠婦女,利用TaqMan等位基因分型技術(shù)對(duì)這兩組人群中HSD11B1 (rs846908)和H5PD(rs6688832和rs17368528)基因位點(diǎn)多態(tài)性進(jìn)行檢測(cè),同時(shí)測(cè)定PCOS患者基礎(chǔ)狀態(tài)下生殖內(nèi)分泌相關(guān)指標(biāo),包括FSH、LH、E2、T、PRL、空腹血糖(Fasting glucose)、空腹胰島素(Fasting insulin)、DHEAS,利用Stata軟件進(jìn)行統(tǒng)計(jì)分析,對(duì)比PCOS組和對(duì)照組各位點(diǎn)基因多態(tài)性之間的差異性,分析PCOS組臨床生化結(jié)果與基因多態(tài)性之間的關(guān)系。[結(jié)果]發(fā)現(xiàn)H6PD基因rs6688832位點(diǎn)多態(tài)性在PCOS組和對(duì)照組中分布存在顯著差異,該位點(diǎn)GG基因型和G等位基因在對(duì)照組中顯著高于PCOS組(P=0.045,P=0.040),說(shuō)明G等位基因是保護(hù)性因素。分析各SNP位點(diǎn)基因型與臨床內(nèi)分泌指標(biāo)之間的關(guān)系,我們發(fā)現(xiàn)PCOS患者rs6688832位點(diǎn)AG基因型與高雄激素血癥顯著相關(guān)(P=0.021),且該位點(diǎn)AG基因型攜帶者比從基因型攜帶者FSH水平低(P=-0.039)。將PCOS組與對(duì)照組按照年齡和體質(zhì)指數(shù)(BMI)進(jìn)行分組進(jìn)行分層分析,結(jié)果發(fā)現(xiàn),rs6688832位點(diǎn)在PCOS組和對(duì)照組中A與G等位基因分布頻率的差異性與年齡無(wú)關(guān)而與BMI有關(guān),在BMI23的超重人群中PCOS組G等位基因頻率顯著降低(P=-0.037),而在BMI≤23的人群中無(wú)顯著性差異。我們未發(fā)現(xiàn)HSD11B1 (rs846908)位點(diǎn)和H6PD (rs17368528)基因位點(diǎn)多態(tài)性與PCOS之間存在顯著關(guān)聯(lián)。[結(jié)論]本研究結(jié)果提示PCOS患者H6PD基因rs6688832位點(diǎn)AG基因型與高雄激素血癥有關(guān),該位點(diǎn)G等位基因是保護(hù)性基因,這種保護(hù)性作用在超重和肥胖人群中體現(xiàn)更明顯。
[Abstract]:[Objective] Kaohsiung is the hormone level of polycystic ovary syndrome (PCOS) in many clinical manifestations of one of the most important features of.17 beta hydroxysteroid dehydrogenase type 5 (HSD17B5) gene and 17 beta hydroxysteroid dehydrogenase type 6 (HSD17B6) gene encoding specific enzymes involved in androgen synthesis and metabolism, and therefore is the key gene and androgen synthesis metabolism. This study evaluated the polymorphisms of HSD17B5 gene and HSD17B6 gene with polycystic ovary syndrome patients. Methods relationship between risk and clinical manifestations] collected from 335 PCOS patients as the research object, the control group was 354 normal pregnant women with type TaqMan allele (AD) of HSD17B5 of the two groups the crowd (rsl937845 and rs12529) and HSD17B6 (rs898611) to detect polymorphism, and compare their differences. At the same time in patients with PCOS were measured under baseline endocrine, metabolic parameters, including eggs Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), fasting blood glucose (Fasting glucose), fasting insulin (Fasting insulin), dehydroepiandrosterone sulfate (DHEAS), Stata software was used for statistical analysis, contrast group and PCOS the differences between the control group and gene polymorphism of PCOS were analyzed. The correlation between clinical and biochemical results with the gene polymorphism we found in the PCOS group and the control group there was a significant difference of HSD17B5 gene rs1937845 locus genotype, the CT genotype and T allele was significantly higher than that of in the PCOS control group (group P=-0.002, P=-0.012 distribution), indicating that the HSD17B5 gene rs1937845 CT genotype and T allele is a susceptible gene of PCOS. We compared the relationship between PCOS patients with HSD17B5 and HSD17B6 index of Clinical Endocrinology polymorphicloci, found HSD17B5 Because of the rs12529 genotype CC in serum testosterone levels were significantly higher than GG genotype (P=-0.034); the rs1937845 gene TT genotype higher testosterone levels than CC genotype (P=-0.053), and the TT genotype in insulin secretion index homeostasis model (HOMA-B%) was significantly higher than that of CC genotype (P=-0.045). The PCOS group according to the testosterone level the level is divided into Kaohsiung hormones group and non hormone group in Kaohsiung, analyzing the relationship between the SNP polymorphism and Kaohsiung hormone level, we found that HSD17B5rs12529 GC genotype (P=-0.054) and C allele (P= -0.002) and rs1937845 (P=-0.047) CT genotype and T allele (P=-0.004 Kaohsiung) were closely related with the hormone level. No HSD17B6 gene rs898611 polymorphism and the correlation between the risk of PCOS. Conclusion] this study suggests that HSD17B5 gene RS polymorphism with PCOS 1937845 The genetic susceptibility, CT genotype and T allele may increase the risk of the risk of PCOS.HSD17B5 may be involved in the regulation of androgen metabolism and the rs12529 gene GC genotype and C allele and rs1937845 CT genotype and T allele increased in PCOS patients in Kaohsiung suffer hormone level risk. Has been found between HSD17B6 gene rs898611 polymorphism and genetic susceptibility of PCOS Association.]PCOS patients often suffer from obesity, abnormal glucose tolerance (or diabetes) and elevated serum insulin levels, body fat distribution and glucose metabolism, lipid metabolism of glucocorticoids involved and play an important role in.11 beta hydroxy hydroxysteroid dehydrogenase type 1 (HSD11B1) is a key enzyme in the regulation of glucocorticoid activity, mainly for nicotinamide adenine dinucleotide phosphate (NADPH) dependent enzyme activity was That H6PD can catalyze the nicotinamide adenine dinucleotide (NAD) reduced to NADPH, the synergistic effect of active glucocorticoid, so HSD11B1 and H6PD are the key genes of sugar, lipid metabolism. Methods in this study. The relationship between glucocorticoid metabolism key genes HSD11B1 and H6PD gene polymorphism and susceptibility to PCOS in this study in group PCOS, 335 patients with PCOS, the control group of 354 pregnant women, the use of HSD11B1 for the two groups in the typing of TaqMan allele (rs846908) and H5PD (rs6688832 and rs17368528) were used to detect gene polymorphism, simultaneous determination of relevant indicators, reproductive endocrine in patients with PCOS in basic condition, including FSH LH, E2, T, PRL (Fasting glucose), fasting blood glucose, fasting insulin (Fasting insulin), DHEAS, Stata software was used for statistical analysis, comparison between PCOS group and control group the difference between the gene polymorphism H6PD, rs6688832 gene polymorphisms have significant differences between PCOS group and control group were found in the PCOS group to analyze the relationship between the clinical biochemical results and gene polymorphism. The results, GG genotype and G allele in control group was significantly higher than that of group PCOS (P=0.045, P, =0.040) G allele is a protective factor. Analyzing the relationship between the SNP genotype and clinical endocrine index, we found that PCOS was significantly correlated with rs6688832 genotype AG and Kaohsiung hormones (P=0.021), and the genotype AG than genotype carriers from low levels of FSH (P=-0.039) and PCOS group. The control group according to the age and body mass index (BMI) were grouped into stratified analysis, results showed that the difference of rs6688832 site in PCOS group and control group in A and G allele frequency distribution has nothing to do with age and is associated with BMI in BMI23 The overweight people in PCOS group, G allele frequency was significantly decreased (P=-0.037), while no significant differences in BMI is less than or equal to 23 of the population. We found no HSD11B1 (rs846908) and H6PD (rs17368528) were correlated significantly. Conclusion] the results suggest that H6PD patients with PCOS gene rs6688832 AG genotype is associated with Kaohsiung hormones between gene polymorphism and PCOS, the G allele is a protective gene, the protective effect of more obvious in overweight and obese people.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R711.75

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7 教授 李玲　醫(yī)學(xué)碩士 劉娟;多毛、月經(jīng)不調(diào)警惕多囊卵巢綜合征[N];家庭醫(yī)生報(bào);2007年

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9 呂武;多囊卵巢綜合征患者要注意減肥[N];衛(wèi)生與生活報(bào);2007年

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